Pediatric Gastroenteritis Medication
- Author: Randy P Prescilla, MD; Chief Editor: Russell W Steele, MD more...
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.[33, 34] A recent meta-analysis found probiotics may be especially effective for the prevention of C difficile –associated diarrhea in patients receiving antibiotics. 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. 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.
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. Recent large trials in both Latin America and Africa have also found Rotarix to be effective in decreasing diarrhea morbidity and mortality in children.[38, 39, 40]
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).
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.
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).
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.
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.
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 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 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 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 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.
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.[42, 43]
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. 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.[42, 45]
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 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 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.
Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010 Jun 5. 375(9730):1969-87. [Medline].
King CK, Glass R, Bresee JS, Duggan C,. Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy. MMWR Recomm Rep. 2003 Nov 21. 52(RR-16):1-16. [Medline].
Dennehy PH. Acute diarrheal disease in children: epidemiology, prevention, and treatment. Infect Dis Clin North Am. 2005 Sep. 19(3):585-602. [Medline].
Hullegie S, Bruijning-Verhagen P, Uiterwaal CS, et al. First-year Daycare and Incidence of Acute Gastroenteritis. Pediatrics. 2016. 137(5):e20153356.
Fischer Walker CL, Perin J, Aryee MJ, Boschi-Pinto C, Black RE. Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review. BMC Public Health. 2012. 12:220. [Medline].
Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis. 2003 May. 9(5):565-72. [Medline].
Boschi-Pinto C, Velebit L, Shibuya K. Estimating child mortality due to diarrhoea in developing countries. Bull World Health Organ. 2008 Sep. 86(9):710-7. [Medline].
Kosek M, Bern C, Guerrant RL. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ. 2003. 81(3):197-204. [Medline].
Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis. 2012 Feb. 12(2):136-41. [Medline].
Cortese MM, Parashar UD,. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2009 Feb 6. 58(RR-2):1-25. [Medline].
Cortes JE, Curns AT, Tate JE, Cortese MM, Patel MM, Zhou F. Rotavirus vaccine and health care utilization for diarrhea in U.S. children. N Engl J Med. 2011 Sep 22. 365(12):1108-17. [Medline].
Leshem E, Moritz RE, Curns AT, Zhou F, Tate JE, Lopman BA, et al. Rotavirus vaccines and health care utilization for diarrhea in the United States (2007-2011). Pediatrics. 2014 Jul. 134(1):15-23. [Medline].
Laidman J. Rotavirus Vaccine Greatly Reduced Healthcare Use. Medscape. Available at http://www.medscape.com/viewarticle/826391. Accessed: 9/15/14.
Payne DC, Vinje J, Szilagyi PG, Edwards KM, Staat MA, Weinberg GA. Norovirus and medically attended gastroenteritis in U.S. children. N Engl J Med. 2013 Mar 21. 368(12):1121-30. [Medline].
Wenneras C, Erling V. Prevalence of enterotoxigenic Escherichia coli-associated diarrhoea and carrier state in the developing world. J Health Popul Nutr. 2004 Dec. 22(4):370-82. [Medline].
Steiner MJ, DeWalt DA, Byerley JS. Is this child dehydrated?. JAMA. 2004 Jun 9. 291(22):2746-54. [Medline].
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. [Medline].
Gorelick MH, Shaw KN, Murphy KO. Validity and reliability of clinical signs in the diagnosis of dehydration in children. Pediatrics. 1997 May. 99(5):E6. [Medline].
Vega RM, Avner JR. A prospective study of the usefulness of clinical and laboratory parameters for predicting percentage of dehydration in children. Pediatr Emerg Care. 1997 Jun. 13(3):179-82. [Medline].
Duggan C, Refat M, Hashem M, Wolff M, Fayad I, Santosham M. How valid are clinical signs of dehydration in infants?. J Pediatr Gastroenterol Nutr. 1996 Jan. 22(1):56-61. [Medline].
World Health Organization. Treatment of diarrhoea: a manual for physicians and other senior health workers, 4th ed. 2005. Available at http://18.104.22.168/LinkFiles/CAH_Publications_manual_physicians.pdf. Accessed: March 26, 2013.
Sandhu BK. Practical guidelines for the management of gastroenteritis in children. J Pediatr Gastroenterol Nutr. 2001 Oct. 33 Suppl 2:S36-9. [Medline].
Practice parameter: the management of acute gastroenteritis in young children. American Academy of Pediatrics, Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis. Pediatrics. 1996 Mar. 97(3):424-35. [Medline].
Fonseca BK, Holdgate A, Craig JC. Enteral vs intravenous rehydration therapy for children with gastroenteritis: a meta-analysis of randomized controlled trials. Arch Pediatr Adolesc Med. 2004 May. 158(5):483-90. [Medline].
Bellemare S, Hartling L, Wiebe N, Russell K, Craig WR, McConnell D. Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials. BMC Med. 2004 Apr 15. 2:11. [Medline].
Freedman SB, Willan AR, Boutis K, Schuh S. Effect of Dilute Apple Juice and Preferred Fluids vs Electrolyte Maintenance Solution on Treatment Failure Among Children With Mild Gastroenteritis: A Randomized Clinical Trial. JAMA. 2016 May 10. 315 (18):1966-74. [Medline].
MacReady N. Juice, Other Drinks Can Manage Mild Gastroenteritis in Children. Medscape Medical News. Available at http://www.medscape.com/viewarticle/862764. May 03, 2016; Accessed: May 27, 2016.
Nager AL, Wang VJ. Comparison of nasogastric and intravenous methods of rehydration in pediatric patients with acute dehydration. Pediatrics. 2002 Apr. 109(4):566-72. [Medline].
Hahn S, Kim S, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children. Cochrane Database Syst Rev. 2002. (1):CD002847. [Medline].
Murphy C, Hahn S, Volmink J. Reduced osmolarity oral rehydration solution for treating cholera. Cochrane Database Syst Rev. 2004. (4):CD003754. [Medline].
Alam NH, Islam S, Sattar S, Monira S, Desjeux JF. Safety of rapid intravenous rehydration and comparative efficacy of 3 oral rehydration solutions in the treatment of severely malnourished children with dehydrating cholera. J Pediatr Gastroenterol Nutr. 2009 Mar. 48(3):318-27. [Medline].
Gregorio GV, Gonzales ML, Dans LF, Martinez EG. Polymer-based oral rehydration solution for treating acute watery diarrhoea. Cochrane Database Syst Rev. 2009. (2):CD006519. [Medline].
Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev. 2004. (2):CD003048. [Medline].
Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Gastroenterol Nutr. 2001 Oct. 33 Suppl 2:S17-25. [Medline].
Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012 Dec 18. 157(12):878-88. [Medline].
Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2012. 6:CD005436. [Medline].
Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006 Jan 5. 354(1):11-22. [Medline].
Linhares AC, Velazquez FR, Perez-Schael I, Saez-Llorens X, Abate H, Espinoza F. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study. Lancet. 2008 Apr 5. 371(9619):1181-9. [Medline].
Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten M, Louw C. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med. 2010 Jan 28. 362(4):289-98. [Medline].
Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM. Effect of rotavirus vaccination on death from childhood diarrhea in Mexico. N Engl J Med. 2010 Jan 28. 362(4):299-305. [Medline].
Phavichitr N, Catto-Smith A. Acute gastroenteritis in children : what role for antibacterials?. Paediatr Drugs. 2003. 5(5):279-90. [Medline].
Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev. 2011. (9):CD005506. [Medline].
Freedman SB, Hall M, Shah SS, Kharbanda AB, Aronson PL, Florin TA, et al. Impact of increasing ondansetron use on clinical outcomes in children with gastroenteritis. JAMA Pediatr. 2014 Apr. 168(4):321-9. [Medline].
Freedman SB, Adler M, Seshadri R, Powell EC. Oral ondansetron for gastroenteritis in a pediatric emergency department. N Engl J Med. 2006 Apr 20. 354(16):1698-705. [Medline].
Borowitz SM. Are antiemetics helpful in young children suffering from acute viral gastroenteritis?. Arch Dis Child. 2005 Jun. 90(6):646-8. [Medline].
|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|
|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|
|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|