Diarrhea in Adults - Infectious Xử trí

MANAGEMENT DECISION

Management of acute gastroenteritis in adults may be decided based on the history and presentation. Fever, vomiting and abdominal pain are sensitive symptoms for diarrhea caused by Campylobacter, E coli, Salmonella, Shigella and rotavirus.

Toxin-Induced Food Poisoning or Viral Gastroenteritis

Toxin-induced food poisoning or viral gastroenteritis should be suspected in those with vomiting as the major presenting symptom.

Bacterial Toxin-Induced Food Poisoning

Bacterial toxin-induced food poisoning is caused by Staphylococcus aureus, B cereus, C perfringens, C botulinum, or ETEC. The incubation period is usually 6-24 hours. Watery diarrhea occurs 2-7 hours after eating the contaminated food. Diarrhea may follow vomiting and is usually not so severe. Abdominal pain may also be present and is usually colicky in nature. Most patients are afebrile and not severely dehydrated unless vomiting or diarrhea is intense. The illness may last for 1-2 days.

Viral Gastroenteritis

Viral gastroenteritis is caused by adenovirus serotype 40/41, astrovirus, human caliciviruses (eg norovirus, sapovirus), and rotavirus. Norovirus is the leading cause of infectious diarrhea in adults and the major cause of foodborne gastroenteritis worldwide. The incubation period is usually between 18-72 hours. This is characterized by the abrupt onset of nausea and abdominal cramps followed by vomiting and/or watery diarrhea. Low-grade fever (37.5-38.5°C) develops in about half of affected individuals. Headache, myalgia, upper respiratory tract symptoms and abdominal pain are common. The illness is usually mild and self-limiting, lasting 24-72 hours.

Traveler’s Diarrhea

Traveler’s diarrhea is usually considered in a person who normally resides in an industrialized region and who travels to a developing country or a person from a developing country who travels to an industrialized region. This may also refer to illness that occurs within 7-10 days after returning home. The prodromal symptoms include nausea/vomiting, cramping abdominal pain and fever. This usually lasts 3-7 days and resolves even without treatment.

Watery Diarrhea

Watery diarrhea is characterized by semi-formed to loose-watery stools without the presence of blood. An acute watery diarrhea usually lasts about 7 days. This is often a clinical presentation of enterotoxin-induced diarrhea; the most common causative agent is ETEC in a non-epidemic situation. The incubation period is 3-5 days.

Cholera

Cholera is associated with epidemic diarrhea; it is highly suggested by severe, profuse, watery diarrhea and dehydration. Other clinical features are a very abrupt onset of acute diarrhea with rapid progression to severe dehydration, and the presence of muscle cramps and vomiting but no fever or abdominal pain. The stools are usually watery, mucoid and colorless with little food residue. Stool microscopy and stool culture should be done in all cases. If cholera is confirmed in non-endemic areas, it should be reported to health authorities. Any case of watery diarrhea in cholera-endemic areas during outbreaks or seasonal epidemics should be treated as cholera and stool cultures should be done in all cases to confirm.

Bloody Diarrhea

For bloody diarrhea, the macroscopic exam of stool contains blood. Patients often have a fever that may last >2 days and may be high (>38.5°C). The patients may initially suffer with watery diarrhea that rapidly changes to dysentery (eg STEC infection). There is also mild dehydration. Dysentery is suggested by frequent passage (10-30 times per day) of small-volume stools that consist of blood, mucus and pus. The patient usually suffers moderate to severe abdominal cramps and tenesmus.

Indications for Specialist Consultation or Hospitalization

The indications for specialist consultation or hospitalization include bloody stools, diarrhea >7 days or frequent and large-volume diarrhea, persistent fever and vomiting, moderate to severe dehydration, altered consciousness, immunocompromised or elderly patients, the presence of poorly controlled chronic medical or concurrent illness, intolerant of oral rehydration, poor nutritional status, social circumstances (eg lives alone or far from a hospital, no access to clean water), the presence of electrolyte abnormalities, the absence of improvement within 48 hours, acute kidney injury or no urine output in preceding 12 hours, and signs of extraintestinal involvement (eg meningitis, pneumonia, sepsis) or other cause (eg hemolytic uremic syndrome). 

ANTIDIARRHEALS

Antidiarrheals may assist in reducing the amount of fluid loss, frequency, and consistency of the stool and shorten the clinical course of diarrhea. This is not recommended for cholera.

Antipropulsives

Antipropulsives are useful in moderate to severe secretory diarrhea by decreasing the frequency and volume of stools. Avoid administering these drugs to patients with self-limiting, uncomplicated, mild to moderate viral acute gastroenteritis or evidence of invasive enteritis (eg high fever, chills, bloody diarrhea, abdominal pain). These agents may induce intestinal stasis and may enhance tissue invasion by the organism or delay their clearance from the bowel. Avoid antipropulsives and antibiotics in patients with suspected or confirmed STEC due to the risk of hemolytic uremic syndrome.

Loperamide

Loperamide is the most commonly used agent for treating acute uncomplicated diarrhea. This is used as adjunctive treatment in patients with moderate to severe traveler's diarrhea. Loperamide has antimotility and antisecretory properties. This is a locally-acting opioid receptor agonist that decreases intestinal wall motility and muscular tone. Studies have shown that it significantly reduces stool volume in traveler's diarrhea.

Diphenoxylate

Diphenoxylate is not as effective as Loperamide and may cause cholinergic side effects (eg headache, drowsiness, euphoria, depression and numbness). Fluid replacement is highly encouraged, as this may mask the volume of lost fluids.

Intestinal Adsorbents

Example drugs: Activated charcoal, Attapulgite, Dioctahedral smectite, Kaolin, Pectin

Intestinal adsorbents appear to have some benefit in traveler’s diarrhea, are well tolerated and are safe to use in pregnancy. These are not effective in patients with febrile bloody diarrhea. These may adsorb toxins produced by toxigenic bacteria and act by preventing their adherence to the intestinal membrane. Efficacy, therefore, depends on early administration prior to toxins adhering to the intestinal wall. These render a more formed stool but do not reduce the net loss of water and electrolytes.

Bismuth Preparations

Bismuth preparations may be given to patients with fever and dysentery. Bismuth subsalicylate has antisecretory, antibacterial and anti-inflammatory effects, and can reduce symptoms in patients with mild diarrhea and viral gastroenteritis. These reduce the number of stools passed and the duration of diarrhea by about 50%. These may interfere with absorption of other drugs (eg Doxycycline).

Racecadotril

Racecadotril is an enkephalinase inhibitor that blocks intestinal fluid secretion without affecting motility. This may be administered to reduce the frequency and duration of patient's diarrhea. Racecadotril is indicated for: Moderate to severe traveler’s diarrhea; moderate to severe dehydration with fever alone, fever and bloody stools, or symptoms of >3 days; invasive bacterial diarrhea with fever and bloody stools in the absence of EHEC; patients suspected of enteric fever and with clinical features of sepsis; high-risk patients (eg immunocompromised, immunosuppressed, extremely young patients and elderly); hospital- or antibiotic-associated diarrhea; patients with underlying illness; and epidemics. Food-borne toxigenic diarrhea usually does not require empiric antibiotic treatment. Modify treatment based on stool culture results if symptoms are not improved with empiric therapy.

Traveler’s Diarrhea

Azithromycin 

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Azithromycin should be considered in areas where Campylobacter and Shigella resistance to quinolones has become problematic. This is reported effective against traveler’s diarrhea in Southeast Asia, where C jejuni is a common cause of diarrhea and quinolone-resistant Campylobacter sp are common.

Quinolones

Quinolones are typically considered the treatment of choice for acute diarrhea in adult travelers but resistant organisms are becoming an issue, especially in Southeast Asia.

Rifaximin

Rifaximin is used for the treatment of traveler’s diarrhea caused by non-invasive strains of E coli. Rifaximin is not absorbed from the GI tract and therefore may not be effective against invasive organisms eg Shigella or Campylobacter spp.

Duration of Therapy

Three days of antibiotic treatment is recommended (Azithromycin, Ciprofloxacin, Levofloxacin or Ofloxacin may be taken as a single dose). Reevaluate the patient after 24 hours of antibiotic treatment. If no improvement is evident, continue to complete 3 days of antibiotic treatment. If the patient is well after 24 hours from the beginning of antibiotic therapy, consider stopping the therapy sooner.

Cholera

Rehydration and antibiotics are the mainstays of therapy in cholera. When antibiotics are administered to cholera patients, there is a reduction in stool volume loss and a shorter clinical course. Antibiotics administered should follow local epidemiological and recent sensitivity data for V cholerae, if available. The first-line agents Azithromycin, Tetracycline, Doxycycline or Ciprofloxacin may be used if sensitivity data is not known. If with Tetracycline resistance, consider Erythromycin ethylsuccinate, Azithromycin or Ciprofloxacin. Many V cholerae strains (0139 and 01 El Tor strains) are resistant to Co-trimoxazole (Sulfamethoxazole [SMZ] and Trimethoprim [TM]) and Furazolidone. The duration of therapy is 3 days except for Azithromycin, Doxycycline, and Ciprofloxacin which are all taken as single doses.

Bloody Diarrhea

Antipropulsives should be avoided, as these drugs may increase the severity by delaying excretion of organisms and facilitating invasion of the mucosa. Empiric antibiotics can reduce the duration of illness and shorten the carrier stage.  Once EHEC or STEC has been excluded by stool exam, empiric therapy with antibiotics can be started. Antibiotics following the local sensitivities for Shigella sp may be used as empiric therapy while waiting for culture and sensitivity results. If local sensitivities are not known, one of the following empiric antibiotics may be used: Azithromycin (first line), Ciprofloxacin, Levofloxacin, or Norfloxacin. The duration of therapy is 3 days.

PATHOGEN-SPECIFIC ANTIBIOTIC TREATMENT

In most cases, antimicrobial therapy is not required since diarrhea is usually self-limited; however, therapy with empiric and specific antibiotics may be given in certain situations: Severe cholera and shigellosis; dysenteric form of campylobacteriosis and non-typhoidal salmonellosis. The choice of antimicrobial therapy should depend on local susceptibility patterns.

Aeromonas and Plesiomonas

Antibiotics are not usually required for Aeromonas and Plesiomonas. For Aeromonas sp, antibiotics may be indicated in patients prone to septicemia (eg cirrhosis, immunocompromised patients). For Plesiomonas sp, antibiotics may be required in severely ill or immunocompromised patients. The first-line agents are quinolones and the second-line agents include Azithromycin, Co-trimoxazole, or Cefixime. The duration of therapy is 3-5 days.

Campylobacter sp

Antibiotics are not usually required for Campylobacter sp but may be used in severely ill patients, immunodeficient patients or patients with traveler’s diarrhea. The first-line agent is Azithromycin and the second-line agents are Quinolones. The duration of therapy is 3-7 days.

E coli 0157:H7 (Enterohemorrhagic, EHEC)

For E coli 0157:H7, avoid antipropulsives and antibiotics.

Salmonella (Non-typhi) sp

Antibiotics are recommended in severe illness, when the patient is septic or hospitalized. Usually, no treatment is needed in asymptomatic or mild illness. The first-line agents are quinolones and the second-line agents are Ceftriaxone, Co-trimoxazole, or Azithromycin. The duration of therapy is 3-14 days. Ceftriaxone may be considered in suspected septicemic cases. Co-trimoxazole should only be used if the organism is susceptible. Avoid antidiarrheal agents as they may prolong the bacterial excretion period or cause paralytic ileus.

Shigella sp

The first-line agents are Azithromycin, third-generation cephalosporins (Ceftriaxone, Cefixime) or quinolones. The susceptibility to Ciprofloxacin should be assessed by minimum inhibitory concentration (MIC) value; fluoroquinolones should be avoided if MIC ≥0.12 mcg/mL. The second-line agents are Co-trimoxazole or Ampicillin; if susceptible, Nalidixic acid. The duration of therapy is 3-5 days depending on the agent used.

Vibrio cholerae

The primary treatment for Vibrio cholerae is aggressive rehydration; antibiotics serve as adjunctive treatment. The first-line agent is Azithromycin and the second-line agents are Ceftriaxone, Ciprofloxacin or Doxycycline. The duration of therapy is 3 days depending on the agent used.

Yersinia sp

Antibiotics are not usually required for Yersinia sp but may be used in severely ill patients, bacteremia or immunocompromised hosts. Abdominal pain caused by mesenteric adenitis can mimic pain of acute appendicitis. The first-line agents are Co-trimoxazole or Ciprofloxacin, and the second-line agents are Cefotaxime, Doxycycline, or Tetracycline. 

Rehydration in Mild Dehydration

Oral Rehydration Therapy (ORT)¹

Oral rehydration therapy is the standard for cost-effective management of acute gastroenteritis. This consists of both rehydration and maintenance fluid therapy. Patients with mild dehydration and little or no vomiting may be rehydrated orally with oral rehydration salt solution (ORS). ORS should be given at 1.5-2 times the volume of stool loss in 24 hours without stopping dietary intake. If vomiting is severe and fluids cannot be replaced orally, IV Ringer’s lactate solution may be given.

Oral Rehydration Salt Solution (ORS)

Oral rehydration salt solution (ORS) is a recommended first-line therapy for mild to moderate dehydration in adults with acute diarrhea from any cause and in patients with mild to moderate dehydration associated with vomiting or severe diarrhea. This achieves optimal oral fluid replacement for moderate to severe dehydration. This may also be used in those with mild dehydration along with intermittent free water intake. This is given after each loose stool (120-240 mL) up to 2 L in 24 hours.

The ORS formula recommended by the World Health Organization (WHO) is 75 mmol/L sodium, 20 mmol/L potassium, 65 mmol/L chloride, 10 mmol/L citrate, 75 mmol/L glucose (anhydrous). This produces less vomiting and diarrhea than other formulas and decreases the need for IV normal saline. This is recommended in all age groups and types of diarrhea including cholera. Rice-based ORS may be used for patients with cholera whenever its preparation is convenient. Homemade oral fluid solution may be an option and consists of a mixture of 1 L clean (boiled then cooled) drinking water plus ½ teaspoon of salt and 6 teaspoons of sugar.

¹Many oral rehydration formulas are available. Please see the latest MIMS for specific formulations and prescribing information.

Rehydration in Moderate to Severe Dehydration

Intravenous (IV) Therapy 

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Patients who present with severe dehydration, mental status changes, ileus or hypovolemic shock should be treated promptly with aggressive IV fluid replacement, if available. Ringer’s lactate solution is preferred since it contains 4 mEq/L of potassium. If Ringer’s lactate solution is unavailable, normal saline solution may be an alternative in all age groups. Assessment of fluid and electrolyte deficit is important in order to calculate the amount to replace. For overweight or obese patients, calculate using the ideal body weight. Stool volume loss should be closely observed and if possible, weighed or measured. In patients with moderate dehydration and vomiting or inability to tolerate orals, at least half of the total calculated loss should be replaced within 4 hours and the rest within 24 hours. In patients with severe dehydration with hypovolemic shock, half of the total calculated loss should be replaced within the first hour and the rest within 4 hours. Ongoing losses should be replaced volume per volume with IV fluid boluses or ORS. If the patient is still hypotensive with signs of beginning congestion, assess for other causes of shock and treat appropriately. A specialist referral may be needed in the rehydration of elderly patients, and patients with kidney disease or heart failure. 

The measures to prevent diarrheal diseases may include the following: Personal measures such as washing of hands with soap before and after eating and after each bowel movement; and drinking clean, boiled and safe (source) water. Population measures include proper human waste and garbage disposal; safe food preparation, processing and handling; and cholera or typhoid vaccination. Educate patients regarding complications such as bowel perforation, renal failure, or septicemia. Patients should eat as tolerated and may consume small meals and low-residue foods.

Traveler’s Diarrhea

A traveler should avoid undercooked food except peeled fruits or vegetables and non-bottled water, beverages and unpasteurized dairy products.

Water Purification

Travelers who are going to be living in rustic circumstances overseas will need to make arrangements for a safe water supply.

Prophylactic Antibiotics

Prophylactic antibiotics are effective but not recommended unless the complications of diarrhea in a traveler or severe dehydration in a person with an underlying medical condition cause the benefits of antibiotic prophylaxis to outweigh the risks. Rifaximin is recommended when antibiotic prophylaxis is indicated; fluoroquinolones are not recommended for prophylaxis.

Bismuth Preparations

Bismuth preparations may have protective efficacy over a 7-day period.

Probiotics

Live microorganisms that have been demonstrated in controlled human studies to confer a health benefit on the host. Interaction of probiotics and normal GI microbiota with the host via metabolic and immune mechanisms results in the prevention of colonization of pathogenic and opportunistic microorganisms. Currently, there is a lack of evidence to recommend the use of any strain of probiotic in the prevention or treatment of acute diarrhea; evidence is currently insufficient to recommend its use in adults. Limited non-randomized control trials suggest Saccharomyces boulardii CNCM I-745 may be used to prevent traveler's diarrhea. The following probiotics may be given for the prevention and treatment of acute infectious diarrhea in adults: Lactobacillus paracasei B 21060, L rhamnosus GG, L reuteri, S boulardii CNCM I-745, a strain of S cerevisiae, and Bifidobacterium lactis.

Cholera

The prevention depends on interruption of fecal-oral transmission as V cholerae is spread through contaminated food and water. Consider tracing the source of infection. Water can be treated with chlorine or iodine, by filtration, or by boiling. Travelers to regions with cholera should follow precautions for the prevention of traveler’s diarrhea. The World Health Organization (WHO) recommends that cholera control programs in endemic areas and areas with cholera outbreaks should include cholera vaccination.