Pediatric Gastroenteritis in Emergency Medicine Medication

Updated: Mar 05, 2019
  • Author: Adam C Levine, MD, MPH; Chief Editor: Kirsten A Bechtel, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and for prophylaxis. Antidiarrheal (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 side effects, including ileus, drowsiness, and nausea. 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. Two large systematic reviews have found probiotics (especially Lactobacillus GG) to be effective in reducing the duration of diarrhea in children presenting with acute gastroenteritis, though most of the included studies focused on patients in the inpatient rather than outpatient setting and included mostly patients in low and middle-income countries. [48, 49]  A more recent randomized trial conducted in the US and Canada found that among children with acute gastroenteritis, those who received a 5-day course of Lactobacillus GG did not have shorter duration of diarrhea or shorter duration of vomit than those who received placebo. [50]  At the same time, another recent meta-analysis found probiotics may be especially effective for the prevention of C difficile –associated diarrhea in patients receiving antibiotics. [51]  As probiotic preparations vary widely, it is difficult to estimate the effectiveness of any single preparation.                          

The World Health Organization (WHO) 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 developed countries, children who are well-nourished (i.e. low risk of zinc deficiency) and children younger than 6 months of age. [52]  In another systematic review, zinc shows effectiveness with moderate quality of evidence for developing countries, where zinc deficiency and malnutrition is prevalent. [53]  Zinc is also inexpensive and has shown cost-effectiveness in developing countries, but is associated with episodes of vomiting, which is a cause for future research. [53]          

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Vaccines

Class Summary

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 a 3-dose series at 2, 4, and 6 months of age. [54]  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. [54]  Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains.

Rotavirus vaccine (RotaTeq, Rotarix)

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. 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. 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 says that immunization should not be deferred and that 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.66

Vaccine efficacy is generally lower in countries with higher level of child mortality (i.e. low- and middle-income countries). 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.

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Antimicrobials

Class Summary

Because most cases of acute gastroenteritis in developed and developing countries 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 E coli). [55, 56]  

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-occurence, severe episode, vancomycin is recommended and the addition of metronidazole IV is optional. For a recurring, severe episode, rifaximin should follow vancomycin. [57]

Metronidazole and tinidazole are first-line drugs and have been found to have similar efficacies, with cure rate up to 90% of patients. Tinidazole has a similar regiment and fewer side 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 is usually reserved for difficult cases because it has numerous side effects. [58]

The WHO in 2017 recommended single-dose azithromycin (20 mg/kg) as a first-line therapy for treating pediatric cholera infection. [59] Antibiotic therapy should be extended to include children presenting with moderate to severe dehydration, especially in resource-constrained settings. Ciprofloxacin and doxycycline have demonstrated increasing resistance and should be used only in settings with documented pathogen susceptibility. Ciprofloxacin is not recommended for children and doxycycline is not recommended for children younger than 8. Erythromycin exhibits more adverse effects than azithromycin.

A prospective, multicenter, double-blind randomized controlled trial found that in children who continues to vomit after the first oral rehydration therapy attempt (ORT), a single dose of ondansetron significantly improved the success of ORT and reduced the need for IV therapy and the number of patients with episodes of vomiting during emergency department stay, compared to a placebo and the drug domperidone. [60]  Another randomized control trial found that rotavirus-infected children treated with ondansetron had fewer diarrhea episodes and fewer days with clinical symptoms. [61]  These trials were conducted in developed countries (Italy and Sweden respectively).

Ondansetron provides the strongest evidence for effectiveness in two systematic reviews. The evidence is less strong or uniform about other antiemetics such as metoclopramide and dimenhydride. There is nonetheless some evidence for metoclopramide and dimenhydride’s effectiveness, but they are believed to have some serious side effects. [62, 63, 64]  The majority of studies included in the reviews focus on children in developed countries. More research is needed to address whether the purported effectiveness of ondansetron is also found in low-resourced settings. Another study conducted in Pakistan by Freedman et al reported that an oral, single dose of ondansetron did not reduce the use of intravenous rehydration and did not improve clinical outcomes in children without dehydration. [65]

Metronidazole (Flagyl)

Recommended as the treatment of choice for mild-to-moderate cases of C difficile colitis. Provides effective therapy, with reported response rates from 95-100%. In vitro activity is bactericidal and dose dependent. Standard dosing has been shown to promote fecal concentrations capable of a 99.99% reduction of C difficile. Metronidazole IV may be administered to those patients who cannot tolerate PO medications because of its potential to accumulate in the inflamed colon. IV route is not as effective as PO.

Nitazoxanide (Alinia)

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

Doxycycline (Bio-Tab, Doryx, Doxy)

Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.

Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Treatment of choice for cholera. Not recommended for children younger than 8 years.

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Antiemetics

Class Summary

A review of 7 randomized, controlled trials in children found that oral ondansetron reduced vomiting and the need for intravenous (IV) rehydration and hospital admission, IV ondansetron and metoclopramide reduced the number of episodes of vomiting and hospital admission, and dimenhydrinate suppository reduced the duration of vomiting. [55, 56]

A previous large, prospective, randomized, double-blind trial compared a single dose of an orally disintegrating ondansetron tablet with placebo in children presenting to an emergency department with acute gastroenteritis. [57] This study also found that children treated with ondansetron were less likely to vomit and that they had greater oral intake, were less likely to require IV rehydration, and had a reduced length of stay in the emergency department compared with children treated with placebo.

Several smaller studies have also demonstrated ondansetron to be effective in children. [55, 58]

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. Off-label indication for pediatrics.

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