Pediatric Gastroenteritis Medication

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.^{[23, 24]} Because probiotic preparations vary widely, estimating the effectiveness of any single preparation is difficult.

One meta-analysis, including 18 published studies, all conducted in developing countries, found zinc supplementation to be effective in reducing the duration and severity of diarrhea in children with acute gastroenteritis.^[25] The WHO recommends zinc supplementation (10-20 mg/d for 10-14 d) for all children younger than 5 years with acute gastroenteritis, though little data exist to support this recommendation for children in developed countries.

Class Summary

In February 2006, the US Food and Drug Administration (FDA) approved the RotaTeq vaccine for prevention of rotavirus gastroenteritis. The vaccine has been endorsed by the American Academy of Pediatrics (AAP).

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.^[26] Recent large trials in both Latin America and Africa have also found Rotarix to be effective in decreasing diarrhea morbidity and mortality in children.^{[27, 28, 29]}

Rotavirus vaccine (RotaTeq, Rotarix)

Currently, 2 orally administered live-virus vaccines are marketed in the United States.^[6] Each is 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 reported that the vaccines prevented 74-78% of all rotavirus gastroenteritis cases, nearly all severe rotavirus gastroenteritis cases, and nearly all hospitalizations due to rotavirus.

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).^[30]

In patients with positive stool assays or high clinical suspicion for C difficile, the offending antibiotic should be stopped immediately. Metronidazole (30 mg/kg/d divided qid for 7 d) can be used as a first-line agent, with oral vancomycin reserved for resistant infections.^[30]

Though generally not recommended for children younger than 8 years, tetracycline (50 mg/kg/d divided qid for 3 d) and doxycycline (6 mg/kg single dose) remain the treatment of choice for cholera. Alternative treatments with good efficacy include erythromycin and ciprofloxacin.^[30]

For patients with ova and parasites confirming infection with Giardia, metronidazole (35-50 mg/kg/d divided q8h) remains the drug of choice. Nitazoxanide oral suspension (aged 1-3 y: 100 mg q12h for 3 d, aged 4-11 y: 200 mg q12h for 3 d) is as effective as metronidazole and has the added benefit of treating other intestinal parasites, such as Cryptosporidium.

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).

Tetracycline (Sumycin)

Treats gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s). Treatment of choice for cholera. Not recommended for children younger than 8 years.

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.

Class Summary

One large, prospective, randomized, double-blind trial compared a single dose of an orally disintegrating ondansetron tablet to placebo in children presenting to an emergency department with acute gastroenteritis.^[31] The study found that children treated with ondansetron were less likely to vomit, had greater oral intake, were less likely to require IV rehydration, and had a reduced length of stay in the emergency department compared to children treated with placebo. Several smaller studies have also shown ondansetron to be similarly effective in children.^{[32, 33]}

Ondansetron (Zofran)

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