Diarrhea%20in%20adults%20-%20infectious Treatment

• Maintenance of adequate intravascular volume and correction of fluid and electrolyte imbalance take precedence over identification of causative agent
• Vital signs, peripheral perfusion, mental status and urine output should be monitored during rehydration 
• Sports drinks are inappropriate for patients with diarrhea and commercial juices or carbonated drinks containing simple sugar at high concentrations should not be given

Rehydration in Mild Dehydration

Oral Rehydration Therapy (ORT)

• The standard for cost-effective management of acute gastroenteritis
  • Consists of both rehydration and maintenance fluid therapy
• Patients with mild dehydration and little or no vomiting may be rehydrated orally with oral rehydration salts solution (ORS)
  • ORS should be given at 1.5-2x 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
• Many oral rehydration formulas are available. Please see the latest MIMS for specific formulations and prescribing information

Oral Rehydration Salt Solution (ORS)

• 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 associates with vomiting or severe diarrhea 
• Achieves optimal oral fluid replacement for moderate to severe dehydration
• May also be used in those with mild dehydration along with intermittent free water intake
  
  • Given after each loose stool (120-240 mL) up to 2 L in 24 hours

• ORS formula that is recommended by the World Health Organization (WHO):
  
  • 75 mmol/L Na, 20 mmol/L K, 65 mmol/L Cl, 10 mmol/L Citrate, 75 mmol/L Glucose (anhydrous)
  • Produces less vomiting and diarrhea than other formulas and decreases the need for IV normal saline
  • 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
• Home-made oral fluid solution may be an option
  
  • Mixture of 1 L clean (boiled then cooled) drinking water plus 1 teaspoon of salt and 8 teaspoons of sugar

Rehydration in Moderate to Severe Dehydration

IV Therapy

• Patients who present with severe dehydration 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 K
  • 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 
• Patients with moderate dehydration and vomiting or inability to tolerate orals should be treated with IV fluid replacement
  • In these patients, 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 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

• Antidiarrheals may assist in reducing amount of fluid loss, frequency and consistency of the stool and shorten the clinical course of diarrhea
  • Not recommended for cholera

Antipropulsives

• Useful in moderate to severe secretory diarrhea by decreasing the frequency and volume of stools
• AVOID administering these drugs in 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

Loperamide

• Most commonly used agent for treating acute uncomplicated diarrhea
  • Used as adjunctive treatment in patients with moderate to severe traveler's diarrhea
• Loperamide has antimotility and antisecretory properties
  • Locally-acting opioid receptor agonist which decreases intestinal wall motility and muscular tone
• Studies have shown that it significantly reduces stool volume in traveler's diarrhea 

Diphenoxylate

• 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 volume of lost fluids

Intestinal Adsorbents

• Eg Attapulgite, Activated charcoal, Kaolin, Pectin, Dioctahedral smectite
• Appear to have some benefit in traveler’s diarrhea, are well tolerated and safe to use in pregnancy
• Not effective in patients with febrile bloody diarrhea
• 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 intestinal wall
  • Renders a more formed stool, but does not reduce the net loss of water and electrolytes

Bismuth Preparations

• May be given in patients with fever and dysentery
• Bismuth subsalicylate has antisecretory, antibacterial and anti-inflammatory effects
• Reduce the number of stools passed and the duration of diarrhea by about 50%
  
  • May interfere with absorption of other drugs (eg Doxycycline)

Racecadotril

• May be administered to reduce the frequency and duration of patient's diarrhea

Empiric Therapy

• Empiric therapy 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 and elderly)
  • Hospital- or antibiotic-associated diarrhea
  • Epidemics

Traveler’s Diarrhea

Empiric antibiotic treatment for traveler’s diarrhea has been the best approach, but its usefulness is being undermined by growing antibiotic resistance in many parts of the world

General Therapy Principles

• The objective of antimicrobial therapy for treatment of traveler’s diarrhea is shortening illness and returning travelers to normal activities
• Eradication of enteropathogens from stool does not predict the clinical benefits of antimicrobial therapy
• Traveler’s diarrhea is typically short-lived and self-limited, but many organisms that cause the infection can be treated with antibiotics
• Choice of therapy should depend on epidemiologic data

Azithromycin

• Should be considered in areas where Campylobacter resistance to quinolones has become problematic
• 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
• May be used in children

Quinolones

• Typically considered the treatment of choice for acute diarrhea in adult travelers but resistant organisms are becoming an issue especially in Southeast Asia

Rifaximin

• Used for treatment of traveler’s diarrhea caused by noninvasive 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 patient is well after 24 hours from beginning of antibiotic therapy, may consider stopping the therapy sooner

Cholera

• Rehydration and antibiotics are the mainstay of therapy
• When antibiotics are administered to cholera patients, there is reduction of stool volume loss and a shorter clinical course
  
  • Antibiotics administered should follow local epidemiological and recent sensitivity data for V cholerae, if available
• First-line agents Azithromycin, Tetracycline, Doxycycline or Ciprofloxacin may be used if sensitivity data is not known
  • If with Tetracycline resistance, may consider Erythromycin ethylsuccinate, Azithromycin or Ciprofloxacin
• Many V cholerae strains (O139 and O1 El Tor strains) are resistant to Co-trimoxazole (Sulfamethoxazole [SMZ] and Trimethoprim [TM]) and Furazolidone
• Duration of therapy: 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 Shiga toxin-producing E coli (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, Norfloxacin
• Duration of therapy: 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 nontyphoidal salmonellosis
•  Choice of antimicrobial therapy should depend on local susceptibility patterns

Aeromonas/Plesiomonas spp

• Antibiotics not usually required
• Aeromonas sp: Antibiotics may be indicated in patients prone to septicemia (eg cirrhosis, immunocompromised patients)
• Plesiomonas sp: Antibiotics may be required in severely ill or immunocompromised patients
• First-line agents: Quinolones
• Second-line agents: Azithromycin, Co-trimoxazole
• Duration of therapy: 3-5 days

Campylobacter sp

• Antibiotics not usually required; may be used in severely ill patients, immunodeficient patients or traveler’s diarrhea
• First-line agent: Azithromycin
• Second-line agents: Quinolones
• Duration of therapy: 3-5 days

E coli 0157:H7 (enterohemorrhagic, EHEC)

• Avoid antipropulsives and antibiotics

Salmonella (non-typhi) sp

• Antibiotics recommended in severe illness, when patient is septic or hospitalized
  
  • Usually, no treatment in asymptomatic or mild illness
• First-line agents: Quinolones
• Second-line agents: Ceftriaxone, Co-trimoxazole, Azithromycin
• Duration of therapy: 3-7 days
• Ceftriaxone may be considered in suspected septicemic cases
• Co-trimoxazole should only be used if organism is susceptible
• Avoid antidiarrheal agents as they may prolong the bacterial excretion period or cause paralytic ileus

Shigella sp

• First-line agents: Azithromycin, third-generation cephalosporins (Ceftriaxone, Cefixime) or Quinolones
  • Susceptibility to Ciprofloxacin should be assessed by minimum inhibitory concentration (MIC) value; fluoroquinolones should be avoided if MIC ≥0.12 mcg/mL
• Second-line agents: Co-trimoxazole or Ampicillin if susceptible, Nalidixic acid
• Duration of therapy: 3-5 days depending on the agent used

Vibrio cholerae

• Primary treatment is aggressive rehydration; antibiotics serve as adjunctive treatment
• First-line agent: Azithromycin
• Second-line agents: Ceftriaxone, Ciprofloxacin or Doxycycline
• Duration of therapy: 3 days depending on the agent used

Yersinia sp

• Antibiotics not usually required; may be used in severely ill patients, bacteremia or immunocompromised hosts
• Abdominal pain caused by mesenteric adenitis can mimic pain of acute appendicitis
• First-line agent: Co-trimoxazole
• Second-line agents: Cefotaxime or Ciprofloxacin, Doxycycline