Spring 2015

DEFINITIONS – IDSA & WGO“Diarrhea” is an alteration in a normal bowel movement characterized by an increase in the water content, volume, or frequency of stools.

In adults, a decrease in consistency (i.e., soft or liquid) and an increase in frequency of bowel movements to >3 stools per day (24 hrs) have often been used as a definition for epidemiological investigations. Diarrhea is defined as daily stools with a mass greater than 15 g/kg for children younger than 2 years and greater than 200 g for children aged 2 years and older.

“Infectious diarrhea” is diarrhea due to an infectious etiology, often accompanied by symptoms of nausea, vomiting, or abdominal cramps. Dysentery describes an infectious diarrhea with visible blood and mucus in the stool.

“Acute diarrhea” is an episode of diarrhea of <14 days in duration.

“Persistent diarrhea” is diarrhea of 14 or more days in duration. Some experts refer to diarrhea that lasts 30 days or more as “chronic.”

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Normal feces contain 60–85% water, and 70–200mL water is lost per day from the body through defecation. In diarrhea, water loss of up to four times this volume per loose stool occurs; sodium and potassium alkaline salts are excreted along with the water, leading to a fall in plasma pH (acidosis), which can have serious metabolic consequences. Fluid and electrolyte losses are increased further if vomiting also occurs.The situation is especially hazardous in babies and young children, as a relatively high proportion of total body weight is lost, and dehydration can occur very rapidly.

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Infectious diarrheaInfectious diarrhea is further classified into non-inflammatory and

inflammatory diarrhea.

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Non-inflammatory diarrheas Inflammatory diarrheas

Generally a less severe illness Generally a more severe illness

Patients present with nonbloody, watery stools; patients are afebrile and without significant abdominal pain.

Patients present with bloody diarrhea, severe abdominal pain, and fever.

Examination of stool specimens does not reveal the presence of fecal white blood cells (WBC) or occult blood.

Examination of stool specimens reveals the presence of large numbers of fecal leukocytes.

Typically caused by rotaviruses, noroviruses, Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, Cryptosporidium parvum, and Giardia lamblia.

Caused by invasive pathogens including Campylobacter jejuni, Shigella species, Salmonella species, Clostridium difficile, Shiga toxin-producing Escherichia coli (STEC), and Entamoeba histolytica.

Most patients require only supportive therapies

Selected persons may benefit from antimicrobial therapy directed at the causative pathogen.

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Classification of Diarrhea by EtiologyAcute diarrhea. Self-limiting lasting 2-3 days but may last up to 2 weeks. Caused by the following:1) Infections. Most common. Viral infections. Rotavirus: affect children under 2 years of age. Onset 1-2 days and lasts 5-8 days. High risk for dehydration. Norwalk virus (Noro virus) affects older children and adults. Onset 1-2 days and lasts for 24-48 hrs. viral infections are not usually associated with pus or blood in stool.

Bacterial infections. Onset within 8 hrs and lasts for few days. Toxigenic bacteria. Release of enterotoxins in small intestines which leads to large-volume stools that are watery or greasy.

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Invasive bacteria results from invasion of colon mucosa which results in dysentery-like diarrhea with an extreme urgency to defecate, abdominal cramping, fever, small volume stools that may contain blood or pus.Protozoal infections. Cause explosive foul smelling large volume watery stools. Thought to be due to invasion of mucosal layer of small intestines. May last for months and therapy should be considered to eradicate the organism.

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2) Diet induced acute diarrhea. Food allergies, high fiber diets, fatty or spicy foods, large amounts of caffeine or milk intolerance.

3) Drug induced acute diarrhea. Examples include parasympathomimitic drugs, digoxin, quinidine, magnesium hydroxide, laxatives.

4) Chronic diarrhea. Lasts more than 4 weeks. Protozoal infections, food, IBS, hyperthyroidism.

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Patient Evaluation: All of the following must be considered before selecting the most appropriate management.

AgeOnset and duration or diarrheaDescription of stoolOther symptomsMedicationsRecent travelMedical history.

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When to refer to a physician

Very young or very old.Bloody stool.High fever (greater than 38.5 ˚C).Dehydration or weight loss greater than 5 % of

total body weight. Signs of dehydration: dry mouth, sunken eyes, crying without tears, dry skin that is less elastic than normal skin.

Duration of diarrhea for more than 5 days.Severe vomiting..

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Treatment.Oral-rehydration solutions. For a child without

dehydration 10 ml/kg or ½-1 cup for each loose stool. For a child who is vomiting administer smaller amounts 1-2 teaspoonfuls every 2-5 minutes as tolerated.

Fluids to be avoided include hypertonic fruit juices, carbonated beverages, caffeine containing beverages.

Oral replacement therapy should contain sodium chloride, potassium chloride, sodium bicarbonate and glucose.

Pharmacologic treatment, including antibiotics for select cases. 16

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Rice-based ORS is superior to standard ORS for adults and children with cholera, and can be used to treat such patients wherever its preparation is convenient.

Rice-based ORS is not superior to standard ORS in the treatment of children with acute non-cholera diarrhea, especially when food is given shortly after rehydration, as is recommended to prevent malnutrition.

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Treatment of children based on the degree of dehydration

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ORT is not intended to stop diarrhea, but acute diarrhea is self-limiting and normally ceases within 24–48 hours. ORT can be recommended for patients of any age, even when referral to a doctor is considered necessary.

An oral rehydration product (Dioralyte Relief [Sanofi-Aventis]) containing powdered rice starch in place of glucose is claimed to achieve even greater rehydration than glucose over time, and the rice starch is claimed to help produce firmer stools, leading to faster recovery compared with glucose.

A Cochrane Review found that polymer (including rice)-based ORS showed some advantages compared with glucose-based ORS for treating diarrhea of any cause.

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The contents of one sachet of ORS should be dissolved in 200mL water; for infants the water should be freshly boiled and cooled. It is important to make up the solution exactly to the recommended volume, as too concentrated a solution will be hyperosmolar, drawing more water into the intestine and exacerbating the diarrhea and dehydration. To avoid risk of possible exposure to further infection, the solution should be discarded not later than 1 hour after reconstitution, or it may be kept for up to 24 hours if stored in a refrigerator.

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The recommended dose of ORS for an adult is 200–400 mL after every loose motion, or 2–4 L over 4–6 hours. (Diabetic patients can use ORS, but they should be reminded to monitor blood glucose levels carefully.) Patients may prefer to sip one or two teaspoonfuls every few minutes rather than drink large quantities less frequently.

Children over 2 years of age should be offered a cupful (200 mL) of solution after each loose stool.

Children under 2 years of age should be offered one-quarter to one-half a cupful. Infants should be given one to one-and-a-half times the normal feed volume.

Both breastfed and formula-fed babies should be fed normally during diarrhea; formula feed should not be diluted.

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Seven Up should really be avoided due to high osmolarity (WHO recommends 245 mmol/L and Seven Up has more than twice that: may

actually aggravate diarrhea!!)

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Antiperistaltic drugs. Act by stimulating mu opioid receptor on the circular and longitudinal smooth muscles of small and large intestines. Loperamide, narcotics, diphenoxylate. Effective in non-specific diarrhea and traveler’s diarrhea. Contraindicated in children less than 2 and not preferred in those less than 6.

Contraindicated in acute invasive bacterial diarrhea. Why??

Shouldn’t be used for more than 48 hrs in acute diarrhea.Adult dose of loperamide: 4 mg initially followed by 2 mg after each unformed stool, not to exceed 8 mg in most patients even though the maximum allowed daily dose is 16 mg daily.

Side effects include dry mouth, dizziness, drowsiness and abdominal pain.

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Products* Loperamide– several brands available* Loperamide with simethicone– Imodium PlusMcNeil

Loperamide (2 mg) is formulated with the surfactant compound simethicone (125 mg) in a chewable tablet. The manufacturers claim that the combined formulation relieves the cramping and bloating that can accompany diarrhoea, and that it improves the effectiveness of loperamide. A study carried out by the manufacturers involving nearly 500 patients has shown that the combination product considerably reduced the duration of diarrhea and relieved gas-related discomfort in comparison with loperamide alone.

The dosage of this product is two tablets initially for adults over 18 years of age (one tablet for young adults aged 12–18 years) followed by one tablet after each loose stool (for all ages from 12 years). The maximum dosage is four tablets daily for 2 days. 26

Other TreatmentsAdsorbents. Kaolin and bismuth subsalicylate.

Probiotics. Lactobacillus. For prevention.

Lactase. For lactose intolerant patients.

Antibiotics. Azithromycin, ciprofloxacin, sulfamethoxazole/trimethoprim, metronidazole, vancomycin. If used to prevent traveler’s diarrhea, start 1 day before and continue until 2 days after departure.

Anticholinergic medications. Atropine, hyoscyamine.

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AdsorbentsThe following compounds are available:* kaolin* pectin* attapulgite* bismuth subsalicylate.

Kaolin is a natural hydrated aluminum silicate that has been used in the treatment of diarrhea since ancient Greek times. It is not absorbed fromthe gastrointestinal tract, and about 90% of the drug is metabolised in the gutand excreted in the feces.

Pectin is a purified carbohydrate obtained from the rind of citrus fruit or pomace (crushed apple); its mode of action is uncertain.

Attapulgite is a naturally occurring clay mineral, consisting of hydrous magnesium aluminum silicate. Its adsorptive capacity can be increased by thermal treatment; the heat-treated form is known as activated attapulgite. In vitro alkaloidal adsorptive studies have shown activated attapulgite to have an adsorptive capacity for certain toxic compounds that is five times greater than that of kaolin. Both kaolin and attapulgite have varying and relatively weak adsorptive properties in respect of diarrhea-producing bacteria. 28

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Background Probiotics are live organisms that are ingested

to provide therapeutic or preventative benefit for the host. The most commonly used are the lactic acid-producing bacteria bifidobacteria and lactobacilli. Probiotics also include the yeast Saccharomyces boulardii. Probiotics are commonly promoted to strengthen the immune defenses.

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Bifidobacteria spp Saccharomyces boulardii

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Probiotics, Beneficial Microbes Beneficial microbes such as bifidobacteria

live in the intestinal ecosystem with potentially pathogenic bacteria. Beneficial microbes prevent the overgrowth of “bad bacteria” by producing antimicrobial agents. Additionally, beneficial microbes competitively limit pathogenic bacterial overgrowth by occupying receptor sites and vying for space and nutrients. Beneficial microbes may also increase intestinal production of mucin, which stimulates the production of mucus, forming a protective barrier on the intestinal lining

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In order to be effective, probiotics must be able to withstand a wide range of pH variation. Many microbes cannot withstand the protective acid barrier of the stomach and the effects of bile. An effective probiotic also must be able to colonize the gut and be able to attach to the intestinal epithelium. Additionally, the probiotic should not disturb healthy intestinal microbes

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Probiotic Bacteria and Yeasts Bifidobacteria are anaerobic, rod-shaped,

gram-positive bacteria. Bifidobacteria are the most prominent beneficial microbes in the colon. Bifidobacteria produce antimicrobial substances that have a broad spectrum of antimicrobial activity

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Bifidobacteria that are commonly used as probiotics include Bifidobacterium longum, B. breve, B. infantis, B. bifidum, B. lactis, and B. adolescentis. Bifidobacteria supplements are most commonly combined with other probiotics. Lactobacilli are a group of gram-positive rods that are obligate and facultative anaerobes. Lactobacilli are in the colon in much lower numbers than bifidobacteria. Lactobacilli also produce a range of antimicrobial agents. Lactobacilli that are commonly used as probiotics are Lactobacillus rhamnosus, L. acidophilus, L. casei, L. reuteri, and L. bulgaricus. Lactobacilli supplements are used alone or in combination with other probiotics.

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Other bacteria sometimes used as probiotics include Streptococcus thermophilus and Leuconostoc species. The yeasts Saccharomyces boulardii and S. cerevisiae are also used

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Probiotics for Diarrhea

Probiotics may be useful as adjunctive treatment of adults and children with infectious diarrhea. Several species of Lactobacillus seem to reduce the duration of diarrhea, particularly in rotaviral infections. For antibiotic-associated diarrhea, Lactobacillus rhamnosus GG, S. boulardii, and probiotic mixtures appear to be effective prophylactic agents. Given along with antibiotics, these probiotics can reduce the incidence of diarrhea by about 60% to 65%. The effectiveness of probiotics on treatment of antibiotic-associated diarrhea is less clear.

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Results of studies looking at probiotics for traveler’s diarrhea have been mixed. Studies using Lactobacillus species have shown very modest or no effect. Combination treatment with L. acidophilus, L. bulgaricus, B. bifidum, and S. thermophilus may be better for reducing the frequency of diarrhea, but there have been no head-to-head comparisons with single agents. S. boulardii also may modestly reduce traveler’sdiarrhea.

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Other Probiotic Uses

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SAFETY

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SUMMARY

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