Pediatric Gastroenteritis in Emergency Medicine

Though often considered a benign disease, acute gastroenteritis remains a leading cause of morbidity and mortality in children around the world. Because the disease severity depends on the degree of fluid loss, accurately assessing dehydration status and appropriately rehydrating patients remains a crucial step in preventing morbidity and mortality. Luckily, most cases of dehydration in children can be accurately diagnosed by a careful clinical examination and treated with simple, cost-effective measures.

 

Adequate fluid balance in humans depends on the secretion and reabsorption of fluid and electrolytes in the intestinal tract; diarrhea occurs when intestinal fluid output overwhelms the absorptive capacity of the gastrointestinal tract. The 2 primary mechanisms responsible for acute gastroenteritis are (1) damage to the villous brush border of the intestine, causing malabsorption of intestinal contents and leading to an osmotic diarrhea, and (2) the release of toxins that bind to specific enterocyte receptors and cause the release of chloride ions into the intestinal lumen, leading to secretory diarrhea.

However, even in severe diarrhea, various sodium-coupled solute co-transport mechanisms remain intact, allowing for the efficient reabsorption of salt and water. By providing a 1:1 proportion of sodium to glucose, classic oral rehydration solution (ORS) takes advantage of a specific sodium-glucose transporter (SGLT-1) to increase the reabsorption of sodium, which leads to the passive reabsorption of water. Rice- and cereal-based ORS may also take advantage of sodium-amino acid transporters to increase reabsorption of fluid and electrolytes.

By far, viruses remain the most common cause of acute gastroenteritis in children, both in high-resource and low-resource settings. In the United States, routine rotavirus vaccination has led to a 60-98% reduction in pediatric rotavirus hospitalization since 2006.[1]  With the continued decline of rotavirus-associated gastroenteritis since the introduction of rotavirus vaccines, noroviruses (Norwalk-like viruses) have become the leading cause of medically attended acute gastroenteritis in children younger than 18 years, accounting for 24,000 hospitalizations, 132,000 emergency department visits, 925,000 outpatient visits, and more than $200 million in treatment costs each year.[2, 3]  Approximately half of the norovirus-related visits involved children aged 6-18 months according to a study from the US Centers for Disease Control and Prevention (CDC).[4, 5, 6]  It has been estimated that norovirus results in $60.3 billion in societal costs per year, with the Americas having the highest cost at $23.5 billion.[7]  Annually, norovirus outbreaks cost approximately $173.5 million, with productivity losses representing 95% and direct medical costs representing 4% of total outbreak costs.[8]

Caliciviruses, astroviruses, and enteric adenoviruses make up the remainder of cases of viral gastroenteritis. For children aged < 2 years, astrovirus and sapovirus were detected significantly more in children with acute gastroenteritis than in age-matched healthy controls in the United States.[9]  Viral gastroenteritis typically presents with low-grade fever and vomiting followed by copious watery diarrhea (up to 10-20 bowel movements per day), with symptoms persisting for 3-8 days.[10]

In high-resource settings, bacterial pathogens account for a small portion, perhaps 2-10%, of all cases of pediatric gastroenteritis. In the United States, the most prevalent bacterial pathogens for children under 19 years of age in 2021 included Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (STEC), Shigella, and Yersinia.[11]  Relative to viral gastroenteritis, bacterial disease is more likely to be associated with high fevers, shaking chills, bloody bowel movements (dysentery), abdominal cramping, and fecal leukocytes.[12]

Globally, diarrhea is responsible for more than 1 billion cases of illness and over half a million deaths among children under 5 years of age each year, with approximately 88% of these deaths occurring in South Asia and sub-Saharan Africa.[13]  Although the prevalence of enteropathogens in both these regions is dependent on age, geography, and seasonality (ie, dry versus rainy seasons), both South Asia and sub-Saharan Africa share common etiologies of acute diarrhea.[13, 14, 15]  Several multisite cohort studies in low-income and middle-income countries found Shigella, Campylobacter jejuni, and enterotoxigenic Escherichia coli (ETEC) to be the most prevalent bacterial pathogens, whereas rotavirus, adenovirus, norovirus, and sapovirus are the most prevalent viral pathogens associated with acute diarrhea.[15, 16, 17, 18, 19, 20]  Shigella and rotavirus were the leading bacterial and viral etiology for diarrhea mortality, respectively, among children under 5 years of age in low- and middle-income countries.[20]

Antibiotic-associated diarrhea (AAD) has become a common complication among children. Although studies have suggested the use of probiotics can reduce the risk of AAD in children, several studies recommend further research.[21, 22]  In children, C difficile has emerged as an important cause of AAD, accounting for 22-30% of AAD cases.[23]  However, rates may be higher, as C difficile testing in infants younger than 1 year of age is not recommended, owing to the high rates of colonization (37%). The rate of colonization decreases as age increases.[24]  Any antibiotic can increase the risk of C difficile infection; however, cephalosporins, fluoroquinolones, clindamycin, and certain penicillins (ie, co-amoxiclav) appear to increase risk the most.[25]          

Parasites remain yet another source of gastroenteritis in young children, with Giardia and Cryptosporidium the most common causes in the United States. Parasitic gastroenteritis generally presents with watery stools but can be differentiated from viral gastroenteritis by a protracted course or history of travel to endemic areas.[10, 26, 27]

Most cases of acute gastroenteritis follow a relatively benign course, with less than 2% of diarrheal episodes progressing to severe disease. Even among children who develop severe diarrhea, mortality is only about 2%. Younger children under 2 years of age tend to be at higher risk for death. In all cases, early and appropriate rehydration can reduce mortality in both high- and low-resource settings.

Parents should be reassured that acute gastroenteritis is generally a benign disease, and in most cases it will improve on its own within 1 week without specific treatment. For children without signs of dehydration who are being discharged home, parents should be told to continue breastfeeding/general feeding of the child, and they can encourage extra fluid intake as long as the child tolerates. Parents should be told to return if their child develops intractable vomiting, signs of more severe dehydration such as irritability or lethargy, sunken eyes, reduced skin pinch, decreased tears, or refusal to drink fluids. Parents should also be told to return if the child develops high fevers, seizures, worsening abdominal pain, or bloody diarrhea, or if the diarrhea continues to persist beyond 1-2 weeks.

The history and physical examination serve two vital functions: (1) differentiating gastroenteritis from other causes of vomiting and diarrhea in children, and (2) estimating the degree of dehydration. In some cases, the history and physical examination can also aid in determining the type of pathogen responsible for the gastroenteritis, though only rarely will this affect management.

• Diarrhea: Duration of diarrhea, the frequency and amount of stools, the time since last episode of diarrhea, and the quality of stools. Frequent, watery stools are more consistent with viral gastroenteritis, whereas stools with blood or mucus are indicative of a bacterial pathogen, and "rice water" diarrhea is typically associated with cholera. Similarly, a long duration of diarrhea (>14 d) is more consistent with a parasitic or noninfectious cause of diarrhea. It is important to note that the WHO definition of diarrhea is 3 or more loose stools per day.

• Vomiting: Duration of vomiting, the amount and quality of vomitus (eg, food contents, blood, bile), and time since the last episode of vomiting. When symptoms of vomiting predominate, one should consider other diseases such as gastroesophageal reflux disease (GERD), diabetic ketoacidosis, pyloric stenosis, acute abdomen, or urinary tract infection.

• Urination: Increase or decrease in frequency of urination measured by number of wet diapers, time since last urination, color and concentration of urine, and presence of dysuria. Urine output may be difficult to determine with frequent watery stools.

• Abdominal pain: Location, quality, radiation, severity, and timing of pain, per report of parents and/or child. In general, pain that precedes vomiting and diarrhea is more likely to be due to abdominal pathology other than gastroenteritis.

• Signs of infection: Presence of fever, chills, myalgias, rash, rhinorrhea, sore throat, cough, known immunocompromised status. These may indicate evidence of systemic infection or sepsis.

• Appearance and behavior: Weight loss, quality of feeding, amount and frequency of feeding, level of thirst, level of alertness, increased malaise, lethargy, or irritability, quality of crying, and presence or absence of tears with crying.

• Antibiotics: History of recent antibiotic use increases the likelihood of Clostridium difficile.

• Travel: History of travel to endemic areas may make prompt consideration of organisms that are relatively rare in the United States, such as parasitic diseases or cholera.

Physical findings are as follows:

• General appearance: Weight, ill appearance, level of alertness, lethargy, irritability as depicted in the video below.

  Child with lethargy/poor general appearance.

• Head, ears, eyes, nose, and throat (HEENT): Presence or absence of tears, dry or moist mucous membranes, and whether the eyes appear sunken as shown in the videos below.

  Child with absent tears.

  Child with sunken eyes.

• Respiratory: Rate and quality of respirations (The presence of deep, acidotic breathing suggests severe dehydration.). See the video below.

  Child with hyperpnea (deep, acidotic breathing)

• Abdomen: Abdominal tenderness, guarding, and rebound, bowel sounds. Abdominal tenderness on examination, with or without guarding, should prompt consideration of diseases other than gastroenteritis.

• Back: Flank/costovertebral angle (CVA) tenderness increases the likelihood of pyelonephritis.

• Rectal: Quality and color of stool, presence of gross blood or mucus

• Skin: Abdominal rash may indicate typhoid fever (infection with Salmonella typhi), whereas jaundice might make viral or toxic hepatitis more likely. The slow return of abdominal skin pinch suggests decreased skin turgor and dehydration (see the video below), while a doughy feel to the skin may indicate hypernatremia.

  Child with slow skin pinch (reduced skin turgor).

Workup of acute gastroenteritis should begin by using elements of the history and physical examination to determine the severity of dehydration, which in turn is used to guide overall management. Although the criterion standard for dehydration in children remains the percentage change between their pre-illness weight and admission weight, an accurate and recent pre-illness weight is rarely available in children presenting with acute gastroenteritis.[28]  Many clinical scales have been developed and recommended over the years for predicting dehydration severity in young children.[28, 29, 30, 31, 32, 33, 34, 35]  However, only the Dehydration: Assessing Kids Accurately (DHAKA) score and the Clinical Dehydration Scale (CDS) have been externally validated against a physiologic criterion standard (see Tables 1 and 2 below). Other clinical scales have shown mixed results in validation studies or have not been validated at all.[36, 37, 38, 39, 40, 41]

The CDS consists of four clinical characteristics: general appearance, eye level, mucous membranes, and presence of tears.[34, 38, 42, 43]  All clinical characteristics are measured on a 3-point ordinal scale, where the patient is given a value of 0, 1, or 2 for each assessment. The CDS is an 8-point rating scale with patients who score a 0 being categorized as having no dehydration, those with a score of 1-4 being categorized as having some dehydration, and those with a score of 5-8 having severe dehydration.[34, 38]  In its initial derivation study at a single hospital in Canada, the CDS had strong discriminatory power for detecting moderate-severe dehydration, with a Ferguson’s d of 0.83.[34]  A validation study conducted at three hospitals in Europe found a strong correlation between the CDS and the criterion standard of percent weight change with rehydration, as well as good reliability with a Kappa score of 0.65 (95% CI, 0.43-0.87).[37, 43]

The DHAKA Score comprises four clinical signs including general appearance, skin pinch, presence of tears, and respiration depth. It was derived in a prospective cohort study of patients under 5 years of age in Dhaka, Bangladesh, and later prospectively validated in both Bangladesh and Zambia.[33, 41, 42]  The DHAKA Score is a 12-point scale in which patients with a score of 0-1 are categorized as having no dehydration, 2-3 some dehydration, and 4-12 severe dehydration.[42]  Each 1-point increase in the DHAKA Score predicts an increase of 0.6% in the percentage dehydration of the child.[42]  Upon external validation in a new cohort of patients in Bangladesh, the DHAKA Score was found to be both accurate and reliable with an ordinal c-index of 0.82 and interclass correlation coefficient of 0.94.[40, 42]  More recently, the DHAKA Score was externally validated in Zambia where it had the highest accuracy for assessing dehydration among several different scores.[33, 43]

 Although concerns have been raised regarding the use of clinical signs for assessing dehydration in children with undernutrition (wasting), one study conducted in Bangladesh found that nutritional status did not impact the accuracy of the DHAKA Score or CDS.[44]

Table 1: Dehydration: Assessing Kids Accurately (DHAKA) Score (Open Table in a new window)

Total: ≥4 severe dehydration, 2-3 some dehydration, 0-1 no dehydration.

Adapted from: External Validation of the DHAKA score and comparison to the current IMCI algorithm for the assessment of dehydration in children with diarrhoea. Lancet Global Health. 2016 Oct;4(10):e744-51.

Table 2: Clinical Dehydration Scale (Open Table in a new window)

Adapted from Parkin PC, Macarthur C, Khambalia A, Goldman RD, Friedman JN. Clinical and laboratory assessment of dehydration severity in children with acute gastroenteritis. Clin Pediatr (Phila). 2010 Mar;49(3):235–9.

The vast majority of children who present with acute gastroenteritis do not require serum or urine tests, as they are unlikely to be helpful in determining dehydration severity. In a meta-analysis of 6 studies, among all laboratory tests only serum bicarbonate (< 17) had statistically significant positive and negative likelihood ratios for detecting moderate dehydration, and these were not better than current clinical prediction models.[45]

Clinically significant electrolyte abnormalities are rare in children with moderate dehydration. However, any child being treated with IVF for severe dehydration should have baseline electrolytes, bicarbonate, and urea/creatinine drawn. Laboratory tests may also be indicated in patients with diarrhea whose history and physical examination suggest etiologies other than infectious gastroenteritis.

Stool culture may be helpful in children presenting with bloody diarrhea or recent travel to a low-resource setting. Children older than 12 months of age with a recent history of antibiotic use should have stool tested for C difficile toxins. Those with a history of prolonged watery diarrhea (>14 days) or travel to an endemic area should have stool sent for ova and parasites or molecular testing for intestinal parasites.

Any child with evidence of systemic infection (ie, sepsis) should have a complete workup, including complete blood count (CBC), stool cultures, and blood cultures. If indicated, urine cultures, chest radiography, and/or lumbar puncture should be performed.

Abdominal films are not indicated in the management of acute gastroenteritis. If the clinician suspects a diagnosis other than acute gastroenteritis based on history and physical examination findings, appropriate imaging modalities should be pursued.

Several studies have evaluated the use of point of care ultrasound for assessing dehydration in children. Whereas ultrasound measurement of carotid flow time was found to be a poor predictor of severe dehydration in children with acute diarrhea, the inferior vena cava to aorta ratio has been shown to be statistically associated with dehydration severity.[46, 47, 48, 49]  However, more recent studies have not found ultrasound of the inferior vena cava to aorta ratio accurate enough to be used as an independent diagnostic tool for measuring dehydration severity in children with acute diarrhea, nor did it offer improvement over the accuracy of clinical examination alone.[50, 51]

Experts agree that appropriate rehydration remains the most important management strategy for acute diarrhea in all populations.[33, 52, 53]  Since treatment options are dependent on dehydration status, accurately assessing and managing dehydration remains the most critical step in preventing morbidity and mortality.[54, 55, 56]  Accurate assessment of dehydration status can reduce the morbidity and mortality that results from inappropriate hydration of patients.[57]  One large meta-analysis of 16 trials including 1545 children with mild-to-moderate dehydration found that, compared with intravenous rehydration, children treated with oral rehydration solution (ORS) had a significant reduction in length of hospital stay and fewer adverse events, including seizures and death. It has been reported that for every 25 children who are started on oral rehydration therapy, one would fail and require intravenous therapy (ie, a 4% failure rate).[57]  As such, initial care in the emergency department should focus on correction of dehydration with the type and amount of fluid given reflecting the degree of dehydration in the child, as assessed using the Clinical Dehydration Scale (CDS) or DeHydration: Assessing Kids Accurately (DHAKA) Score described in the workup section.

Minimal or no dehydration

For children assessed as having minimal to no dehydration, no immediate treatment is required. Expectant management of the child can be conducted at home and parents should be provided instructions for continued oral intake.[35, 33, 52, 58]

If the child is breastfed, the mother should be encouraged to breastfeed more frequently than usual and for longer at each feed. If the child is not exclusively breastfed, then oral maintenance fluids (including clean water, soup, rice water, yogurt drink, or other culturally appropriate fluid) should be given at a rate of approximately 500 mL/day for children younger than 2 years, 1000 mL/day for children aged 2-10 years, and 2000 mL/day for children older than 10 years. Ongoing fluid losses should be replaced with 10 mL/kg body weight of additional ORS for each loose stool and 2 mL/kg body weight of additional ORS for each episode of emesis (both for breastfed and non-breastfed children). A study of 647 children in Canada by Freedman et al (2016) found that minimally dehydrated patients with mild gastroenteritis experienced fewer treatment failures when offered half-strength apple juice followed by their preferred drinks, compared with children given a standard electrolyte maintenance solution.[59]  As a result, fewer children administered apple juice required subsequent IV rehydration.

Mild-to-moderate dehydration

Children diagnosed as having mild-to-moderate dehydration should be given oral rehydration solution (ORS) and be managed in an ambulatory clinical setting.[57, 60, 61]  In fact, ORS in particular has been credited with saving more than 50 million lives over the past 50 years.[60, 61]

Over the first 2- to 4-hour period, 50-100 mL/kg of ORS should be given to children to replace their estimated fluid deficit, with additional ORS given to replace ongoing losses (10 mL/kg body weight for each stool and 2 mL/kg body weight for each episode of emesis). ORS should be given slowly by the caregiver or parent using a teaspoon, syringe, or medicine dropper at a rate of 5 mL every 1-2 minutes. If tolerated by the patient, the rate of ORS delivery can be increased slowly over time. After the initial rehydration phase, patients may be transitioned to maintenance fluids as described above. Patients should be reassessed frequently by the clinician to ensure adequacy of oral intake and resolution of the various signs and symptoms of dehydration.

For patients who do not tolerate ORS by mouth, nasogastric (NG) feeding is a safe and effective alternative. Multiple clinical trials have found NG rehydration to be as efficacious as intravenous rehydration, but more cost-effective and with fewer adverse events and shorter hospital stay.[62]

Severe dehydration

Children with severe dehydration require immediate resuscitation with intravenous fluids (IVF) in a hospital to prevent hemodynamic compromise, organ ischemia, and death.[33, 35, 52, 58]  Intravenous access should be obtained, and patients should be administered a bolus of 20-30 mL/kg lactated Ringer's (LR) or normal saline (NS). If pulse, perfusion, and/or mental status do not improve, a second bolus should be administered. After this, the patient should be given an infusion of 70 mL/kg LR or NS over 5 hours (children < 12 months) or 2.5 hours (older children). If no peripheral veins are available, an intraosseous line should be placed. Serum electrolytes, bicarbonate, urea/creatinine, and glucose levels should be measured. Once resuscitation is complete and severe dehydration has resolved, rehydration should continue with ORS as described above.

Type of ORS

A large CochraneDatabase of Systematic Reviews meta-analysis confirmed several earlier studies showing that reduced osmolarity ORS (osmolarity: 245 mmol/L; sodium: 75) is associated with fewer treatment failures, lower stool output, and less frequent vomiting, compared with standard osmolarity ORS for patients with noncholera gastroenteritis.[63]  However, patients with cholera appear to have higher rates of hyponatremia with reduced osmolarity ORS compared with standard osmolarity ORS, without any of the added benefits seen in patients with noncholera gastroenteritis. Nonetheless, the WHO 2005 guideline assessed that the reduced osmolarity solution appeared to be as safe and at least as effective as the standard solution for use in children with cholera. 

Multiple preparations of reduced osmolarity ORS are available in the United States, including Pedialyte, Infalyte, and Naturalyte. Available formulations in Europe include Dioralyte and Diocalm Junior. In developing countries, clinicians can use WHO reduced osmolarity ORS sachets or a homemade solution of 3 g (1 teaspoon) salt and 18 g (6 teaspoon) sugar added to 1 liter of clean water.

A systematic Cochrane review by Gregorio et al (2016) found that polymer-based ORS, made from complex carbohydrates such as rice, wheat, or maize, shows advantages compared to glucose-based ORS with osmolarity over 310 mmol/L. Polymer-based ORS may reduce stool output in the first 24 hours and the duration of diarrhea, albeit supported by low quality of evidence.[64]  Comparisons also favored polymer-based ORS over ORS with osmolarity less than 270 mmol/L, but this analysis is underpowered according to the authors. The possible mechanism of polymer-based ORS is that carbohydrates are slowly digested in the small intestine, releasing glucose to facilitate sodium uptake without adding a significant osmotic load to bowel contents. Although currently not widely available in the United States, polymer-based ORS may become the preferred solution for oral rehydration of children with diarrhea in the future.

Feeding and nutrition

In general, children with gastroenteritis should be returned to a normal diet as rapidly as possible. Early feeding reduces illness duration and improves nutritional outcome.

Breastfed infants should continue breastfeeding throughout the rehydration and maintenance phases of acute gastroenteritis. Formula-fed infants should restart feeding at full strength as soon as the rehydration phase is complete (ideally in 2-4 hours). Weaned children should restart their normal fluids and solids as soon as the rehydration phase is complete. Fatty foods, foods high in simple sugars, commercial carbonated beverages, commercial fruit juices, and sweetened tea should be avoided.

There is a lack of research into the benefits of lactose-free formulas over lactose-containing formulas or the benefits of highly specific diets, such as the BRAT (bananas, rice, applesauce, and toast). Eating only a BRAT diet may provide suboptimal nutrition for patients.

Guidelines by various organizations on pediatric gastroenteritis:

The American Academy of Pediatrics (2012)

The European Society of Pediatric Gastroenterology (2014) and Nutrition (ESPGAN)

The Center for Disease Control (CDC) (2003)

The World Health Organization (2004)

 

The rotavirus vaccine is used for prevention of enterovirus is part of the CDC recommended childhood vaccines. Antimicrobial agents may be necessary to treat specific infections. Examples and discussion of these follows below. 

Probiotics 

Probiotics are live microbial feeding supplements commonly used in the treatment and prevention of acute diarrhea. Possible mechanisms of action include synthesis of antimicrobial substances, competition with pathogens for nutrients, modification of toxins, and stimulation of nonspecific immune responses to pathogens. Several studies have found probiotics to be effective in reducing the duration of diarrhea and stool frequency in children presenting with acute gastroenteritis.[65, 66, 67, 68]  However, two large randomized controlled trials conducted in the US and Canada found that among preschool children with acute gastroenteritis, those who received a 5-day course of Lactobacillus rhamnosus GG did not have improvement in severity or duration of symptoms.[69, 70]  As probiotic preparations vary widely, it is difficult to estimate the effectiveness of any single preparation. Given the current conflicting evidence, probiotics cannot be recommended for routine management of acute diarrhea in children.    

Zinc 

The World Health Organization recommends zinc supplementation (10-20 mg/day for 10-14 days) for all children younger than 5 years with acute gastroenteritis. According to one systematic review, little data exist to support this recommendation for children in high resource settings, children who are well-nourished (ie, at low risk for zinc deficiency), and children younger than 6 months of age.[71] In another systematic review, zinc shows effectiveness with moderate quality of evidence in low resource settings, where zinc deficiency and undernutrition remain prevalent.[72] Zinc is also inexpensive and cost-effective for use in low resource settings but can be associated with increased vomiting.[72]   

Antidiarrheal agents

Antidiarrheals (ie, kaolin-pectin) and antimotility agents (ie, loperamide) are contraindicated in the treatment of acute gastroenteritis in children because of their lack of benefit and increased risk of adverse effects, including ileus, drowsiness, and nausea.

Class Summary

Currently, 2 orally administered live-virus vaccines are marketed in the United States. Each is indicated to prevent rotavirus gastroenteritis, a major cause of severe diarrhea in infants. In February 2006, the US Food and Drug Administration (FDA) approved the RotaTeq vaccine for prevention of rotavirus gastroenteritis. The American Academy of Pediatrics (AAP) has endorsed the vaccine and recommended that the vaccine be administered as an oral 3-dose series at 2, 4, and 6 months of age.[73]  RotaTeq is a pentavalent vaccine that contains 5 live reassortant rotaviruses and protects against G1, G2, G3, and G4 serotypes, the 4 most common rotavirus group A serotypes. It also contains attachment protein P1A (genotype P[8]).

In April 2008, the FDA approved Rotarix, another oral vaccine, for prevention of rotavirus gastroenteritis. The current AAP recommendation is to administer 2 separate doses of Rotarix to infants at 2 and 4 months of age.[73]  Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains.

The AAP expressed no preference for either RotaTeq or Rotarix. The first dose of rotavirus vaccine should be administered before the child is 15 weeks of age. The minimum interval between doses of rotavirus vaccine is 4 weeks. All doses should be administered by 8 months.[73]  While ideally the same vaccine should be used for each dose, in a clinical setting where it is not possible to obtain a product, the AAP states that immunization should not be deferred, and a mixed vaccine schedule can be utilized. A 2016 randomized study supports this recommendation, concluding that mixed schedules for rotavirus vaccines are safe and effective compared to single vaccine schedules.[74, 75]  A 2019 case-control vaccine effectiveness study reported that implementation of rotavirus vaccines has reduced diarrhea-related healthcare use in US children by 86%.[76]

Vaccine efficacy is generally lower in countries with higher level of child mortality (ie, low- and middle-income countries).[75]  However, both vaccines are effective against rotavirus gastroenteritis across a range of mortality settings and different nations. In middle- and low-income countries, it is particularly important that patients receive the full schedule of vaccination.[75, 77, 78, 79, 80]  

Rotavirus oral vaccine, live (Rotarix, RotaTeq)

Live, attenuated oral vaccine indicated for immunization to prevent rotavirus gastroenteritis in infants and children. RotaTeq is administered as a 3-dose regimen, whereas Rotarix is a 2-dose regimen. 

Class Summary

Because most cases of acute gastroenteritis are due to viruses, antibiotics are generally not indicated. Even in cases (eg, dysentery) where a bacterial pathogen is suspected, antibiotics may prolong the carrier state (Salmonella) or may increase the risk of hemolytic uremic syndrome (enterohemorrhagic Escherichia coli).[81, 82]  However, antimicrobials are indicated for a few specific etiologies of diarrhea. 

 

Clostridium difficile

In patients with positive stool assays or high clinical suspicion for C difficile, the offending antibiotic should be stopped immediately. For non-severe episodes, either metronidazole or vancomycin is recommended, with insufficient evidence to recommend one over the other. For a first-occurrence severe episode, vancomycin is recommended and the addition of intravenous metronidazole is optional. For a recurring severe episode, rifaximin should follow vancomycin.[83]

 

Giardia

Metronidazole and tinidazole are first-line drugs and have been found to have similar efficacies, with a cure rate of up to 90% of patients. Tinidazole has a similar regimen and fewer adverse effects. Albendazole and nitazoxanide are second-line drugs and might be difficult to obtain or not licensed in some countries. Paromomycin is the only second-line drug that can be used for pregnant women, and quinacrine (not available in the United States) is usually reserved for difficult cases because it has numerous adverse effects.[84]

 

Vibrio cholerae

The WHO recommends rehydration as the mainstay therapy for the full clinical spectrum of cholera cases. Those with mild to moderate symptoms can be treated successfully with prompt administration of oral rehydration solution (ORS) and in children by providing zinc in addition to ORS. Patients diagnosed with severe dehydration require administration of intravenous fluids, with ORS also administered as soon as oral intake is possible. Antibiotic use should be selective and target those patients most likely to benefit clinically. This includes suspected cholera patients hospitalized with severe dehydration and, regardless of degree of dehydration, those who exhibited high purging or failed the first 4-hour course of rehydration therapy or have comorbidities that pose elevated risk in cholera illness. Antibiotics with proven single-dose efficacy are highly preferred to multidose regimens. For children aged younger than 12 years, a single dose of doxycycline (2-4 mg/kg PO) is recommended. Alternative drug choices include single dose azithromycin (20 mg/kg PO; maximum 1 g) or single dose ciprofloxacin (20 mg/kg PO; maximum 1 g). Zinc supplementation should be given to all children aged 6 months to 5 years with diarrhea.[85]  

 

Shigella dysenteriae

For children, ciprofloxacin (15 mg/kg PO BID for 3 days) is the first-line antibiotic for treatment of Shigella. Pivmecillinam (20 mg/kg PO QID for 5 days; not available in the United States), ceftriaxone (50-100 mg/kg IM QD for 2-5 days), and azithromycin (6-20 mg/kg PO QD for 1-5 days) are also recommended; however, they should only be used when local strains of Shigella are known to be resistant to ciprofloxacin. When an effective antimicrobial is given, improvement should be evident within 48 hours, including fewer stools, less blood in the stools, reduced fever, and improved appetite. Failure to show such improvement may suggest possible antimicrobial resistance. Antibiotics that should not be used for treatment of infections with Shigella owing to its resistivity include ampicillin, chloramphenicol, co-trimoxazole, tetracycline, and nalidixic acid. Nitrofurans, aminoglycosides, first- and second-generation cephalosporins, and amoxicillin may be sensitive to Shigella in vitro but penetrate the intestinal mucosa poorly.[86]  

Vancomycin (Firvanq, Vancocin)

Indicated for Clostridium difficile-associated diarrhea. 

Metronidazole (Flagyl, Flagyl ER, Flagyl IV RTU)

Indicated for severe Clostridium difficile-associated diarrhea. Also indicted as first-line treatment of giardiasis. 

Rifaximin (Xifaxan)

Indicated for Clostridium difficile-associated diarrhea. 

Tinidazole (Tindamax)

Indicated as first-line treatment of giardiasis. 

Albendazole (Albenza)

Indicated as second-line treatment of giardiasis. 

Nitazoxanide (Alinia)

Indicated as second-line treatment of giardiasis. 

Paromomycin

May be considered for off-label use to treat giardiasis. 

Doxycycline

Indicated as single-dose treatment of Vibrio cholera.

Azithromycin (Zithromax, Zmax)

Indicated as single-dose treatment of Vibrio cholera. Also indicated for treatment of Shigella dysenteriae. 

Ciprofloxacin (Cipro, Cipro XR, ProQuin XR)

Indicated as single-dose treatment of Vibrio cholera. Also indicated as first-line treatment of Shigella dysenteriae. 

Ceftriaxone

Indicated for treatment of Shigella dysenteriae. 

Class Summary

Vomiting is a common symptom of acute gastroenteritis; 75% of children with rotavirus infection reported at least one episode.[87]  A prospective, multicenter, double-blind randomized controlled trial (RCT) found that in children who continue to vomit after the first oral rehydration therapy (ORT) attempt, a single dose of the antiemetic ondansetron significantly improved the success of ORT, reduced the need for intravenous therapy, and reduced the number of patients with episodes of vomiting during an emergency department stay, compared with a placebo and the drug domperidone.[88]  Another RCT found that rotavirus-infected children treated with ondansetron had fewer diarrhea episodes and fewer days with clinical symptoms.[89]  A third RCT found that ondansetron was effective in reducing the emesis from gastroenteritis during administration of oral rehydration in the emergency department and in lowering the rates of intravenous fluid administration and hospital admission.[90]  Similarly, two RCTs (one in Pakistan and the other in India) found that administration of ondansetron in dehydrated children with acute gastroenteritis resulted in a reduction of intravenous use, faster rehydration, and fewer vomiting episodes.[91, 92]

There is limited evidence on the efficacy of other antiemetics, such as metoclopramide and dimenhydrinate.[93]  Although some studies have suggested that metoclopramide and dimenhydrinate are effective in reducing vomiting in children with acute gastroenteritis, they are believed to have more severe adverse effects than oral ondansetron.[94, 95]

Ondansetron

May be consider a single oral dose for severe, acute vomiting associated with gastroenteritis.  

Inpatient admission should be considered for all children with acute gastroenteritis in the following situations:

• Signs of severe dehydration are present

• Caregivers are unable to manage oral rehydration or provide adequate care at home

• Substantial difficulties exist in administering oral rehydration, such as intractable vomiting

• Failure of treatment occurs, such as worsening diarrhea or dehydration, despite adequate fluid intake

• Factors are present necessitating closer observation, such as young age, decreased mental status, or uncertainty of diagnosis

• Children with mild-moderate dehydration, age < 6 months, or high frequency of stools/vomits should be monitored in the emergency department for a minimum of 4-6 hours before discharge

The US Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommend routine vaccination of US infants with rotavirus vaccine to protect against rotavirus gastroenteritis.

Parents should be instructed to continue providing maintenance fluids at home as needed. Breastfeeding and formula feeding should be continued for infants, and children should be encouraged to return to a regular diet as rapidly as possible.

Parents should be instructed to look for the various signs of dehydration outlined above, such as change in mental status, decreased urine output, sunken eyes, absence of tears, dry mucous membranes, and slow return of abdominal skin pinch.

Parents should seek medical attention if dehydration returns, oral intake is inadequate, or if their child develops worsening abdominal pain, temperature >101ºF (38.3ºC), or prolonged diarrhea lasting longer than 14 days.