eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Diarrhea

Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston; M Akram Tamer, MD, Program Director, Professor, Department of Pediatrics, University of Miami

Updated: Jan 5, 2009

Introduction

Background

Acute diarrhea is defined as the abrupt onset of abnormally high fluid content in the stool (more than the normal value of approximately 10 mL/kg/d). This situation typically implies an increased frequency of bowel movements, which can range from 4-5 to more than 20 times per day. The augmented water content in the stools 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; however, numerous disorders may cause this condition, 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); 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, according to the formula: ion gap = osmolality – [(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 assumes a cumulative incidence of 1 hospitalization for diarrhea per 23-27 children by age 5 years, with more than 50,000 hospitalizations in 2000. By these estimates, rotavirus is associated with 4-5% of all childhood hospitalizations, and 1 in 67 to 1 in 85 children are hospitalized due to rotavirus by age 5 years. 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.

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. 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 still remains high.

Because the single most common cause of infectious diarrhea worldwide is rotavirus, and because a vaccine has been in use for over 2 years now, a reduction in the overall frequency of diarrheal episodes is hoped for in the near future.

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.

Furthermore, in countries where 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.

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 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.

Clinical

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, fever, 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 found that the highest incidence of acute diarrhea was in January and August, with an overall incidence of 2.21 episodes per person-year.¹ 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 4 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

Stool Characteristics	Small Bowel	Large Bowel
Appearance	Watery	Mucoid and/or bloody
Volume	Large	Small
Frequency	Increased	Highly increased
Blood	Possibly positive but never gross blood	Commonly grossly bloody
pH	Possibly <5.5	>5.5
Reducing substances	Possibly positive	Negative
WBCs	<5/high power field	Commonly >10/high power field
Serum WBCs	Normal	Possible leukocytosis, bandemia
Organisms	Viral Rotavirus Adenovirus Calicivirus Astrovirus Norovirus	Invasive bacteria Escherichia Coli (enteroinvasive, enterohemorrhagic) Shigella species Salmonella species Campylobacter species Yersinia species Aeromonas species Plesiomonas species
	Enterotoxigenic bacteria E coli Klebsiella Clostridium perfringens Cholera species Vibrio species	Toxic bacteria Clostridium difficile
	Parasites Giardia species Cryptosporidium species	Parasites Entamoeba organisms

• 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

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
Norovirus	1-2 d	2 d	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	1 d	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
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

• 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.
  • 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
• 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
• 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

• 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.
• 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

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 acute diarrhea 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
    • 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
  • 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
    • Calicivirus - 1-20% of cases
    • Norovirus - 10% 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

Differential Diagnoses

Workup

Laboratory Studies

• 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.
• 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 3. Common Bacteria and Optimum Culture Mediums

Organism	Detection Method	Microbiologic Characteristics
Aeromonas species	Blood agar	Oxidase-positive flagellated gram-negative bacillus (GNB)
Campylobacter species	Skirrow agar	Rapidly motile curved gram-negative rod (GNR); Campylobacter jejuni 90% and Campylobacter coli 5% of infections
C difficile	Cycloserine-cefoxitin-fructose-egg (CCFE) agar; enzyme immunoassay (EIA) for toxin; latex agglutination (LA) for protein	Anaerobic spore-forming gram-positive rod (GPR); toxin-mediated diarrhea; produces pseudomembranous colitis
C perfringens	None available	Anaerobic spore-forming GPR; toxin-mediated diarrhea
E coli	MacConkey eosin-methylene blue (EMB) or Sorbitol-MacConkey (SM) agar	Lactose-producing GNR
Plesiomonas species	Blood agar	Oxidase-positive GNR
Salmonella species	Blood, MacConkey EMB, xylose-lysine-deoxycholate (XLD), or Hektoen enteric (HE) agar	Nonlactose non–H2S-producing GNR

• 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 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.

Procedures

• Intestinal biopsy: This procedure 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 new recommendations for the management of acute pediatric diarrhea in both the outpatient and inpatient settings including indication for referral.²
 
Indications for medical evaluation of children with acute diarrhea include the following: 

• Older than 3 months
• Weight of more 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
• 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

• 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 ORS must be viewed as by far the safest, most 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.³ 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 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.

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.
• 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

• 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.

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.

• 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.

Medication

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).² 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:
  • 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 (lactic acid bacteria or mycetes thought to benefit the host in some circumstances when ingested in adequate doses) 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 little more than one day and seems to be exerted mostly on rotoviral diarrhea, with lack of 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. 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.

Currently, estimates suggest that rotavirus infections cause over 50,000 hospital admissions annually in the United States alone. 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.

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).’’⁴

Antibiotic and antiparasitics agents

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.

Dosing

Adult

400 mg/d PO qd for 7-10 d

Pediatric

8 mg/kg/d PO qd for 7-10 d

Interactions

Aminoglycosides increase nephrotoxic potential; probenecid may increase effects by decreasing clearance

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Documented hypersensitivity to penicillins; reduced renal function; administer with food to minimize nausea and diarrhea

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.

Dosing

Adult

1-2 g IV/IM q24h

Pediatric

50 mg/kg/d IV/IM divided qd/bid for 7-10 d; not to exceed 2 g/d

Interactions

Probenecid increases ceftriaxone serum concentration

Contraindications

Documented hypersensitivity; do not use in neonates who are hyperbilirubinemic

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with allergies to penicillin antibiotics; may cause skin rashes, diarrhea, and pain at site of injection

Cefotaxime (Claforan)

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

Dosing

Adult

1-2 g IV/IM q6-8h for 7-10 d

Pediatric

50 mg/kg/dose IV/IM tid for 7-10 d

Interactions

Probenecid may increase levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with allergies to penicillin antibiotics; may cause rashes, thrombophlebitis, and GI upset (eg, nausea, vomiting, diarrhea)

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.

Dosing

Adult

250-500 mg (base, stearate, or estolate) PO qid
400-800 mg (ethylsuccinate) PO qid

Pediatric

50 mg/kg/d PO/IV divided qid for 7-10 d

Interactions

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis

Contraindications

Documented hypersensitivity; hepatic impairment; inhibits CYP3A4, caution with concomitant administration of CYP3A4 substrates (eg, terfenadine, cisapride, astemizole)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occurs

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.

Dosing

Adult

100 mg PO qid for 7-10 d

Pediatric

5 mg/kg/d PO divided qid for 7-10 d

Interactions

Increases levodopa blood concentrations and, thus, potential for toxicity; causes disulfiramlike reactions when taken with alcohol; toxicity of meperidine, paroxetine, fluoxetine, sertraline, trazodone, MAOIs, sympathomimetic amines, and TCAs increases when taken with furazolidone

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in G-6-PD deficiency when administering prolonged treatments; inhibits enzyme monoamine oxidase; may cause rashes, thrombophlebitis, and GI upset (eg, nausea, vomiting, diarrhea)

Iodoquinol (Vytone, Yodoxin)

Antiparasitic agents with wide coverage.

Dosing

Adult

650 mg PO tid pc for 20 d

Pediatric

30-40 mg/kg/d PO divided tid pc for 20 d; not to exceed adult dose

Interactions

None reported

Contraindications

Documented hypersensitivity; preexisting optic neuropathy or hepatic damage

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid long-term use; commonly causes nausea, vomiting, stomach pain, and diarrhea

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).

Dosing

Adult

250-500 mg PO tid for 10 d

Pediatric

30-50 mg/kg/d PO divided tid for 10 d; not to exceed adult dose

Interactions

May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiramlike reaction may occur with orally ingested ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not use in pregnancy during first trimester; adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

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.

Dosing

Adult

25-30 mg/kg/d PO divided tid for 7 d; not to exceed 4 g/d

Pediatric

Administer as in adults

Interactions

Nephrotoxic potential may increase with concurrent administration of other aminoglycosides, penicillins, cephalosporins, amphotericin B, and loop diuretics

Contraindications

Documented hypersensitivity; intestinal obstruction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Because of narrow therapeutic index and toxic hazards associated with extended administration, do not use for long-term therapy; caution in renal failure, hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Quinacrine (Atabrine)

Very effective antiparasitic against Giardia species.

Dosing

Adult

100 mg PO tid for 5-7 d

Pediatric

6 mg/kg/d PO divided tid for 5 d

Interactions

Can cause disulfiram-type reaction when mixed with alcohol

Contraindications

Documented hypersensitivity; psoriasis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hemolysis (frequently dose-related) may occur in individuals who are G-6-PD deficient; may cause nausea, vomiting, abdominal pain, anorexia, and diarrhea; eczematous eruptions and discoloration of skin; poor palatability

Sulfamethoxazole and trimethoprim (Bactrim, Septra, Cotrim)

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.

Dosing

Adult

160 mg (based on trimethoprim component) PO bid for 7-10 d

Pediatric

10 mg/kg/d (based on trimethoprim component) PO bid for 7-10 d

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly individuals; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency; age <2 mo

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at first appearance of rash or sign of adverse reaction; frequently obtain CBC counts; discontinue if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; caution in folate deficiency (eg, persons with chronic alcoholism, elderly individuals, those receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in individuals who are G-6-PD deficient; patients with AIDS may not tolerate or respond; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

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.

Dosing

Adult

500 mg PO qid for 10-14 d

Pediatric

40-50 mg/kg/d PO divided qid for 10-14 d; not to exceed 2 g/d

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

IV preparation requires dose adjustment for renal failure, but PO form is poorly absorbed

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.

Dosing

Adult

250-500 mg PO q6h
Mild-to-moderate infections: 500 mg PO bid or 250 mg PO qid for 7-14 d
Severe infections: 500 mg PO qid for 7-14 d

Pediatric

<8 years: Not recommended
>8 years: 25-50 mg/kg/d (10-20 mg/lb) divided PO qid

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants

Contraindications

Documented hypersensitivity; severe hepatic dysfunction

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

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.

Dosing

Adult

500 mg PO bid for 3 d

Pediatric

<1 year: Not established
1-3 years: 100 mg (5 mL) PO q12h for 3 d with food
4-11 years: 200 mg (10 mL) PO q12h for 3 d with food
>11 years: Administer as in adults

Interactions

Tizoxanide (nitazoxanide metabolite) is >99.9% bound to plasma protein and may potentially increase toxicity of other highly plasma protein–bound drugs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause abdominal pain, diarrhea, vomiting, or headache; administer with food; caution when coadministered with other highly plasma protein–bound drugs with narrow therapeutic indices

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.

Dosing

Adult

200 mg PO tid

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Induces CYP450 3A4 in vitro; limited data exist; no significant interactions shown in single dose studies with midazolam and oral contraceptives

Contraindications

Documented hypersensitivity to rifaximin or rifamycin antimicrobial agents (eg, rifampin)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May promote intestinal bacterial overgrowth and cause superinfection; discontinue if diarrhea persists more than 24-48 h or worsens; seek immediate medical care if fever and/or bloody stools emerge (tablets not effective); not effective for travelers' diarrhea due to suspected pathogens other than E coli; postmarketing reports include allergic dermatitis, rash, angioneurotic edema, urticaria, and pruritus

Vaccines

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]).
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.

Dosing

Adult

Not indicated

Pediatric

<6 weeks: Not established
RotaTeq
6-12 weeks: 2 mL PO as a single dose, followed by 2 additional doses at 4- to 10-wk intervals; do not administer after age 32 wk
Rotarix
6 weeks: 1 mL PO as a single dose; administer a second dose after an interval of at least 4 wk and before 24 wk of age

Interactions

Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, high-dose corticosteroids) may decrease immune response

Contraindications

Documented hypersensitivity; uncorrected congenital GI malformation that would predispose to intussusception

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include diarrhea, vomiting, otitis media, inflamed nasal passages, and bronchospasm; refrigerate and protect from light; handle and discard empty tube according to biological waste procedures; previously marketed rotavirus vaccine (RotaShield) was associated with intussusception; however, RotaTeq did not show an increased risk compared with placebo in clinical trials (monitor for signs of intestinal blockage), and Rotarix did not show an increase in intussusception in 31,673 infants compared with 31,552 infants who received placebo; do not mix in same syringe with other vaccines or solutions; febrile illness may be reason for delaying use except when, in the opinion of the physician, withholding the vaccine entails a greater risk; low-grade fever (<100.5°F [38.1°C]) itself and mild upper respiratory infection do not preclude vaccination

Follow-up

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.

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.

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). It is currently the only vaccine approved in the United States for prevention of rotavirus gastroenteritis as of the date of this publication. On February 21, 2006, 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.⁵
• 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

  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, 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.
  • 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 excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Diarrhea.

  References

  1. Vernacchio L, Vezina RM, Mitchell AA, Lesko SM, Plaut AG, Acheson DW. Diarrhea in American infants and young children in the community setting: incidence, clinical presentation and microbiology. Pediatr Infect Dis J. Jan 2006;25(1):2-7. [Medline].

  2. King CK, Glass R, Bresee JS, Duggan C. Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy. MMWR Recomm Rep. Nov 21 2003;52:1-16. [Medline].

  3. Guarino A, Albano F, Ashkenazi S, et al. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: executive summary. J Pediatr Gastroenterol Nutr. May 2008;46(5):619-21. [Medline].

  4. Guandalini S. Probiotics for children with diarrhea: an update. J Clin Gastroenterol. Jul 2008;42 Suppl 2:S53-7. [Medline].

  5. [Best Evidence] Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. Jan 5 2006;354(1):11-22. [Medline]. [Full Text].

  6. Abubakar I, Aliyu SH, Arumugam C, Usman NK, Hunter PR. Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis. Br J Clin Pharmacol. Apr 2007;63(4):387-93. [Medline].

  7. Bellemare S, Hartling L, Wiebe N, et al. Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials. BMC Med. Apr 15 2004;2:11. [Medline]. [Full Text].

  8. Bryce J, Boschi-Pinto C, Shibuya K, Black RE,. WHO estimates of the causes of death in children. Lancet. Mar 26-Apr 1 2005;365(9465):1147-52. [Medline].

  9. Charles MD, Holman RC, Curns AT, et al. Hospitalizations associated with rotavirus gastroenteritis in the United States, 1993-2002. Pediatr Infect Dis J. Jun 2006;25(6):489-93. [Medline].

  10. Coffin SE, Elser J, Marchant C, et al. Impact of acute rotavirus gastroenteritis on pediatric outpatient practices in the United States. Pediatr Infect Dis J. Jul 2006;25(7):584-9. [Medline].

  11. Girard MP, Steele D, Chaignat CL, Kieny MP. A review of vaccine research and development: human enteric infections. Vaccine. Apr 5 2006;24(15):2732-50. [Medline].

  12. Guandalini S. Treatment of acute diarrhea in the new millennium. J Pediatr Gastroenterol Nutr. May 2000;30(5):486-9. [Medline].

  13. Guandalini S, Dincer AP. Nutritional management in diarrhoeal disease. Baillieres Clin Gastroenterol. Dec 1998;12(4):697-717. [Medline].

  14. Guandalini S, Kahn S. Acute diarrhea. In: Walker A, Goulet O, Kleinman J, et al eds. Pediatric Gastrointestinal Disease. Vol 1. Ontario, Canada: Brian C. Decker; 2008:252-64/Chapter 15.

  15. Sandhu BK, Isolauri E, Walker-Smith JA, et al. A multicentre study on behalf of the European Society of Paediatric Gastroenterology and Nutrition Working Group on Acute Diarrhoea. Early feeding in childhood gastroenteritis. J Pediatr Gastroenterol Nutr. May 1997;24(5):522-7. [Medline].

  16. Sullivan PB. Nutritional management of acute diarrhea. Nutrition. Oct 1998;14(10):758-62. [Medline].

  17. Walker-Smith JA, Sandhu BK, Isolauri E, et al. Guidelines prepared by the ESPGAN Working Group on Acute Diarrhoea. Recommendations for feeding in childhood gastroenteritis. European Society of Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. May 1997;24(5):619-20. [Medline].

  Keywords

  diarrhea, loose stool, runny stool, fluid stool, acute gastroenteritis, traveler's diarrhea, dysentery, dehydration, childhood diarrhea, malabsorption, malabsorption syndrome, acute-onset diarrhea, inflammatory bowel disease, irritable bowel syndrome, toddler's diarrhea, rotavirus, hemolytic uremic syndrome, HUS, chronic diarrhea, viral diarrhea, rotavirus, adenovirus, astrovirus, liver disease, achlorhydria, hemolytic anemia, sickle cell disease, malaria, agammaglobulinemia, pancreatitis, cystic fibrosis, calicivirus, yersinia enterocolitis, Yersinia enterocolitica, Aeromonas, Shigella, Escherichia coli, E coli, Clostridium, Salmonella, Giardia, Cryptosporidium, Entamoeba

  Contributor Information and Disclosures

  Author

  Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
  Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition
  Disclosure: Nothing to disclose.

  Coauthor(s)

  Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston
  Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and International Neuropsychological Society
  Disclosure: Nothing to disclose.

  M Akram Tamer, MD, Program Director, Professor, Department of Pediatrics, University of Miami
  M Akram Tamer, MD is a member of the following medical societies: American Medical Association and Florida Medical Association
  Disclosure: Nothing to disclose.

  Medical Editor

  Chris A Liacouras, MD, Director of Pediatric Endoscopy, Department of Pediatrics, Division of Gastroenterology and Nutrition, Associate Professor, Children's Hospital of Philadelphia and University of Pennsylvania
  Chris A Liacouras, MD is a member of the following medical societies: American Gastroenterological Association
  Disclosure: Nothing to disclose.

  Pharmacy Editor

  Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
  Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

  CME Editor

  Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health
  Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
  Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership

  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, and Royal College of Physicians and Surgeons of Canada
  Disclosure: Nothing to disclose.

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