Medication Summary
The goals of pharmacotherapy are to reduce morbidity, prevent complications, and provide 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 adverse 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. [38, 39] A meta-analysis found probiotics may be especially effective for the prevention of C difficile –associated diarrhea in patients receiving antibiotics. [40] As probiotic preparations vary widely, it is difficult to estimate the effectiveness of any single preparation.
A recent review of 24 published studies found zinc supplementation may be effective in reducing the duration of diarrhea in children older than 6 months in areas where zinc deficiency and moderate malnutrition is prevalent. [41] 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, although little data exist to support this recommendation for children in developed countries.
The mainstay of therapy includes prevention with the rotavirus vaccine and treatment with antimicrobials and antiemetics.
Vaccines
Class Summary
In February 2006, the US Food and Drug Administration (FDA) approved the RotaTeq vaccine for the 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 the 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. [42] Recent large trials in both Latin America and Africa have also found Rotarix to be effective in decreasing diarrhea morbidity and mortality in children. [43, 44, 45]
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.
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 weeks.
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.
Antibiotics
Class Summary
Since the majority of cases of acute gastroenteritis in developed and developing countries are due to viruses, antibiotics are generally not indicated. Even in cases (eg, dysentery) in which a bacterial pathogen is suspected, antibiotics may prolong the carrier state (Salmonella infection) or may increase the risk of developing hemolytic-uremic syndrome (enterohemorrhagic Escherichia coli infection). [46]
In patients with positive stool assays or high clinical suspicion for C difficile infection, the offending antibiotic should be stopped immediately. Metronidazole (30 mg/kg/day divided qid for 7 days) can be used as a first-line agent, with oral vancomycin reserved for resistant infections. [46]
Although generally not recommended for children younger than 8 years, tetracycline (50 mg/kg/day PO divided qid for 3 days) and doxycycline (6 mg/kg PO as a single dose) remain the treatments of choice for cholera. Alternative treatments with good efficacy include erythromycin and ciprofloxacin. [46]
For patients with ova and parasite testing that confirms infection with Giardia, metronidazole (35-50 mg/kg/day PO divided q8h) remains the drug of choice. Nitazoxanide oral suspension (age 1-3 y: 100 mg PO q12h for 3 days; age 4-11 y: 200 mg PO q12h for 3 days) is as effective as metronidazole and has the added benefit of treating other intestinal parasites, such as Cryptosporidium.
Metronidazole (Flagyl)
Metronidazole is recommended as the treatment of choice for mild-to-moderate cases of C difficile colitis. It 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. IV metronidazole may be administered to those patients who cannot tolerate oral medications because of its potential to accumulate in the inflamed colon. The IV route is not as effective as the oral route.
Doxycycline (Bio-Tab, Doryx, Doxy)
Doxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
It inhibits protein synthesis and, thus, bacterial growth by binding to the 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
It is the treatment of choice for cholera. It is not recommended for children younger than 8 years.
Nitazoxanide (Alinia)
Nitazoxanide inhibits growth of C parvum sporozoites and oocysts and G lamblia trophozoites. It elicits antiprotozoal activity by interference with the pyruvate: ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism. It is available as an oral suspension (20 mg/mL).
Tetracycline (Sumycin)
Tetracycline treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s). It is the treatment of choice for cholera. It is not recommended for children younger than 8 years.
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 d uration of vomiting. [47, 48]
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. [49] 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. [47, 50]
Ondansetron (Zofran)
Ondansetron is a selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. This is an off-label indication for pediatrics. Caution is advised with IV administration because of reported QT prolongation with higher doses.
Metoclopramide (Reglan)
Metoclopramide blocks dopamine receptors in chemoreceptor trigger zone of CNS and sensitizes tissues to acetylcholine. This is an off-label indication for pediatrics. Use is limited because of its risk for tardive dyskinesia.
Dimenhydrinate (Dramamine)
Dimenhydrinate is an ethanolamine H1 antagonist containing diphenhydramine and 8-chloro-theophylline. Its pharmacological effects principally result from diphenhydramine moiety, and it has CNS depressant, anticholinergic, antiemetic, antihistamine, and local anesthetic effects.
Tables
Symptom or Sign |
No or Minimal Dehydration |
Mild-to-Moderate Dehydration |
Severe Dehydration |
Mental status |
Alert |
Restless, irritable |
Lethargic, unconscious |
Thirst |
Drinks normally |
Drinks eagerly |
Drinks poorly |
Heart rate |
Normal |
Normal to increased |
Tachycardia |
Quality of pulses |
Normal |
Normal to decreased |
Weak or not palpable |
Breathing |
Normal |
Normal or fast |
Deep |
Eyes |
Normal |
Slightly sunken |
Deeply sunken |
Tears |
Present |
Decreased |
Absent |
Mouth and tongue |
Moist |
Dry |
Parched |
Skin fold |
Instant recoil |
Recoil < 2 seconds |
Recoil >2 seconds |
Capillary refill |
Normal |
Prolonged |
Prolonged or minimal |
Extremities |
Warm |
Cool |
Cold, mottled, cyanotic |
Urine output |
Normal |
Decreased |
Minimal |
Severe Dehydration |
Two of the following signs:
|
Some Dehydration |
Two of the following signs:
|
No Dehydration |
Not enough of the above signs to classify as some or severe dehydration |
