ACUTE DIARRHEA IN ADULT - INFECTIOUS

Definition

Diarrhea: Change in normal bowel movements characterized by increase in frequency, water content or volume of stools ≥3 episodes/day or at least 250 g/stool per day
Acute diarrhea: Diarrhea lasting <14 days duration
Persistent diarrhea: Diarrhea lasting ≥14 days
Chronic diarrhea: Diarrhea lasting ≥30 days
Infectious diarrhea: Diarrhea of infectious origin (bacterial, viral, protozoal) & is usually associated w/ symptoms of nausea & vomiting (N/V) & abdominal cramps

Clinical Evaluation

Objective:

• Severity of the illness
• The need for rehydration
• Identification of likely causes

Symptoms:

• Determine abrupt or gradual onset, duration & progression of symptoms
• Onset & frequency of bowel movement
• Amount of stool excreted
• If dysenteric symptoms are present (eg fever, tenesmus, blood/pus in stool)

Associated Symptoms

Frequency & intensity of N/V, abdominal pain, cramps, myalgia, headache, altered sensorium

Stool Characteristics

Watery, bloody, mucus, purulent, greasy

Symptoms of Volume Depletion:

• Thirst
• Tachycardia
• Orthostasis
• Decreased urination
• Lethargy

Risk Factors:

• Travel to developing country
• Ingestion of unsafe foods (i.e. raw meats, eggs, shellfish, etc.)
• Swimming/drinking untreated fresh water
• Visit to farm or contact w/ pets or animals
• Contact w/ other ill persons
• Recent or regular medications (eg antibiotics, antacids, antimotility agents)
• Underlying medical conditions [acute immunodeficiency syndrome (AIDS), immunosuppressants, elderly]
• Receptive anal or oral-anal sexual contact

Phx

Focus on evaluating the patient’s hydration status

Vital Signs:

• Pulse rate >90 bpm
• Absence or weak palpable pulse
• Postural or supine hypotension
• Fever

Signs of Volume Depletion

• Dry mucous membranes
• Sunken eyeballs
• Decreased skin turgor
• Absent jugular venous pulsation
• Altered sensorium

Differential Diagnosis

These conditions may present as acute diarrhea w/ or w/o signs of peritonitis & should be excluded in the patient presenting w/ acute diarrhea

• Appendicitis
• Adnexitis
• Diverticulitis
• Inflammatory bowel disease (IBD)
• Ischemic enterocolitis/Mesenteric infarction
• Peritonitis secondary to bowel perforation
• Systemic infections

Management Decisions

Management of acute gastroenteritis in adults may be decided upon the history & presentation

Toxin-Induced Food Poisoning or Viral Gastroenteritis

Should be suspected in those w/ vomiting as the major presenting symptom

Bacterial Toxin-Induced Food Poisoning

• Diarrhea occurs 2-7 hr after eating the contaminated food
• Diarrhea may follow vomiting & is usually not so severe
• Abdominal pain may also be present & is usually colicky in nature
• Most patients are afebrile & not severely dehydrated unless vomiting or diarrhea is intense

Viral Gastroenteritis

• Caused by rotavirus, human caliciviruses, adenovirus serotype 40/41, norovirus
• Characterized by the abrupt onset of nausea & abdominal cramps followed by vomiting &/or diarrhea
• Low-grade fever (above 37.5°C) develops in about half of affected individuals
• Headache, myalgia, upper resp tract symptoms & abdominal pain are common
• Illness is usually mild & self-limiting, lasting 24-48 hr

Traveler’s Diarrhea

• Usually considered in a person who normally resides in an industrialized region & who travels to a developing country or a person from a developing country who travels to an industrialized region
• May also refer to illness that occurs w/in 7-10 days after returning home
• Prodromal symptoms include N/V, cramping abdominal pain & fever
• Usually lasts 3-5 days & resolves even w/o treatment
• Further work-up is required if there is fever or bloody stool
• Bacteria are responsible for 80-90% of cases, parasites in 10%, & viruses in 5-8% of cases

Watery Diarrhea

• Semi-formed to loose-watery stools w/o the presence of blood
• Often clinical presentation of enterotoxin-induced diarrhea; most common causative agent is enterotoxigenic E coli (ETEC) in a non-epidemic situation

Etiology

• Severe dehydration w/ severe watery diarrhea is most likely caused by Vibrio cholerae subgroup O1
• Vibrio O139, other non-O1 vibrios & occasionally Vibrio parahaemolyticus, Aeromonas sp & enteropathogenic Escherichia coli can cause a similar clinical picture (though diarrhea by these organisms is usually milder)

Cholera

1. Associated w/ epidemic diarrhea, it is highly suggested by severe, profuse, watery diarrhea & dehydration
2. Other clinical features: Very abrupt onset of acute diarrhea w/ rapid progression to severe dehydration, presence of muscle cramps & vomiting but no fever or abdominal pain
3. Stools are usually watery, mucoid & colorless w/ little food residue
4. Stool microscopy & stool culture should be done in all cases
5. If cholera is confirmed in nonendemic areas, it should be reported to health authorities
6. Any case of watery diarrhea in cholera-endemic areas during outbreaks or seasonal epidemics should be treated as cholera & stool cultures should be done in all cases to confirm

Bloody Diarrhea
Macroscopic exam of stool contains blood

Etiology

• Shigella spp: Most common cause of acute bloody diarrhea
• S dysenteriae & S flexneri may cause a more severe disease w/ high fever, the former producing Shiga toxin
• S boydii & S sonnei cause a milder disease
• Campylobacter jejuni infection is suggested by a history of exposure to cattle & poultry or the presence of animals near the patient’s cooking area
• Salmonella enteritidis, Yersinia enterocolitica, Clostridium difficile, enterohemorrhagic E coli (EHEC) & enteroinvasive E coli (EIEC) can also produce bloody diarrhea

Clinical Presentation

• Patients often have fever that may last >2 days & may be high (>38.5°C)
• May initially suffer w/ watery diarrhea that rapidly changes to dysentery
• Mild dehydration

Dysentery

1. Suggested by frequent passage (10-30 times per day) of small-volume stools that consist of blood, mucus & pus
2. Patient usually suffers abdominal cramps & tenesmus

Diagnostic tests

• Lab studies are not usually needed but may be helpful in epidemics in etiology identification
• Microbiological testing is not typically required in patients who present <24 hr after the onset of diarrhea unless patients who present w/ blood, pus in stool, are febrile or dehydrated
• Serum creatinine & electrolyte levels should be taken in cases of dehydration or systemic toxicity

Stool Exam

• Stools typical of cholera are watery, mucoid & colorless w/ little food residue (rice-watery stools)
• Bloody mucoid diarrhea is characteristic of EIEC infection, while EHEC produces bloody diarrhea w/ hemorrhagic colitis & hemolytic uremic syndrome in 6-8%

Stool Microscopy

• Performed in cases of persistent or severe bloody diarrhea
• Viral gastroenteritis: Red & white cells are not normally found
• Cholera: May reveal bacteria w/ darting motility but no WBC or RBC
• Yersinia enterocolitica & Clostridium difficile produce heme-positive stool
• No fecal WBC is seen w/ EHEC infection
• Fecal WBCs are present in 80-90% of diarrhea caused by Shigella or Salmonella & are less common w/ those caused by Campylobacter &Yersinia

Stool Culture/Sensitivity

Not necessary for all cases of diarrhea unless a bacterial cause is suspected

Specific Indications

• Bloody stools or those that are positive for occult blood or leukocyte
• W/ severe abdominal pain
• Prolonged diarrhea not previously treated w/ antibiotics
• Immunocompromised host or patient is >70 yr old
• C difficile-associated disease is suspected
• For epidemiologic purposes (eg cases involving food handlers)

Rehydrate & Maintain Hydration

• Maintenance of adequate intravascular volume & correction of fluid & electrolyte imbalance take precedence over identification of causative agent
• Sports drinks are inappropriate for patients w/ diarrhea & commercial juices or carbonated drinks containing simple carbohydrates at high concentrations should not be given

Rehydration in Mild Dehydration

Oral Rehydration Therapy

• Cost-effective
• Patients w/ mild dehydration & little or no vomiting may be rehydrated orally w/ oral rehydration salts soln (ORS)
• ORS should be given at 1.5 x the volume of stool loss in 24 hr w/o stopping dietary intake
• If vomiting is severe & fluids cannot be replaced orally, Ringer’s lactate may be given IV

Oral Rehydration Salts Soln

• May also be used in those w/ mild dehydration along w/ intermittent free water intake
• Given after each loose stool (120-240 mL) up to 2 L in 24 hr
• 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 & diarrhea than standard ORS & decreases the need for IV therapy
• Recommended in all age groups & types of diarrhea including cholera
• Rice-based ORS may be used for patients w/ 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 tsp of salt & 8 tsp of sugar

Clinical Presentation of Moderate Dehydration

• Patient is usually weak or lethargic, irritable, restless, thirst is increased but able to walk or sit
• Able to perform daily activities but w/ limitations (eg not going to work)
• Patient is usually tachycardic w/ normal or slightly decreased systolic blood pressure (SBP) & may or may not have postural hypotension
• Jugular venous pressure is normal or slightly flat, mucosa is slightly dry, there is a fair amount of skin turgor & eyeballs are only minimally sunken

Clinical Presentation of Severe Dehydration

• Patient is inactive, unable to sit or walk, has decreased consciousness, unable to drink w/ reduced urine output
• Unable to perform daily activities, patient stays in bed or needs hospitalization
• Patient is tachycardic, SBP is decreased by >20 mmHg & postural hypotension is present
• Jugular veins are flat, mucosa is severely dry, skin turgor is poor & eyeballs are visibly sunken

Rehydration in Moderate to Severe Dehydration

IV Therapy

• Patients who present w/ severe dehydration or hypovolemic shock should be treated promptly w/ aggressive IV fluid replacement, if available
• Ringer’s lactate is preferred since it contains 4 mEq/L of K
• If Ringer’s lactate is unavailable, normal saline may be an alternative in all age groups
• In patients w/ moderate-severe dehydration, at least half of the calculated loss should be replaced w/in 4 hr & the rest w/in 24 hr
• Total fluid deficit in severely dehydrated patients can be replaced w/in the 1st 4 hr of therapy, half w/in the 1st hr

ANTIDIARRHEALS

Not recommended for cholera

Antipropulsives

• Useful in mild-moderate secretory diarrhea by decreasing the frequency & volume of stools
• Avoid administering these drugs in patients w/ evidence of invasive enteritis (eg high fever, chills, bloody diarrhea, abdominal pain)
• These agents may induce intestinal stasis & may enhance tissue invasion by the organism or delay their clearance from the bowel

Loperamide

• Most commonly recommended agent for treating acute uncomplicated diarrhea
• Actions: Loperamide has antimotility & antisecretory properties

Diphenoxylate

• Not considered as effective as Loperamide & may cause cholinergic side effects

Intestinal Adsorbents

• Appear to have some benefit in traveler’s diarrhea, are well tolerated & safe to use in pregnancy
• Not effective in patients w/ febrile bloody diarrhea
• Eg Attapulgite, Activated charcoal, Kaolin, Pectin, Dioctahedral smectite
• Actions: In theory, may adsorb toxins produced by toxigenic bacteria & 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 & electrolytes

Bismuth Preparations

• May be given in patients w/ fever & dysentery
• Actions: Bismuth subsalicylate has antisecretory, antibacterial & anti-inflammatory effects
• Effects: Reduces the number of stools passed & the duration of diarrhea by about 50%
• May interfere w/ absorption of other drugs (eg Doxycycline)

Empiric Therapy

Empiric therapy is indicated for:

• Moderate to severe traveler’s diarrhea
• Invasive bacterial diarrhea w/ fever & bloody stools in the absence of EHEC
• High-risk patients (eg immunocompromised & 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

• Eradication of enteropathogens from stool does not predict the clinical benefits of antimicrobial therapy
• Traveler’s diarrhea is typically short-lived & self-limited, but many organisms that cause the infection can be treated w/ antibiotics
• Choice of therapy should depend on epidemiologic data

Epidemiology

• Causes of acute traveler’s diarrhea will vary from one geographical area to another
• Toxigenic E coli is one of the most frequently identified organisms
• Campylobacter infections seem to predominate as the cause of traveler’s diarrhea in North Africa & Southeast Asia
• Other common organisms:
• Enteroaggregative E coli, Salmonella, Shigella spp & viruses (eg rotavirus & the Norwalk agent)
• Parasites should be considered in diarrhea that lasts >7 days

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 & 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 esp in Southeast Asia

Rifaximin

• Approved by United States Food & Drug Administration (USFDA) for treatment of traveler’s diarrhea caused by noninvasive strains of E coli
• Rifaximin is not absorbed from the GI tract & therefore may not be effective against invasive organisms eg Shigella or Campylobacter spp

Duration of Therapy

• Three days of antibiotic treatment is recommended (except for Azithromycin taken as a single dose)
• Reevaluate the patient after 24 hr of antibiotic treatment
• If no improvement is evident, continue to complete 3 days of antibiotic treatment
• If patient is well after 24 hr from beginning of antibiotic therapy, may consider stopping the therapy sooner

Cholera

• Rehydration & antibiotics are the mainstay of therapy
• Antibiotics administered should follow local epidemiological & recent sensitivity data for Vibrio cholera, if available
• First-line agents Azithromycin, Tetracycline, Doxycycline or Ciprofloxacin may be used if sensitivity data is not known
• If w/ Tetracycline resistance, may consider Erythromycin ethylsuccinate, Azithromycin or Ciprofloxacin
• Co-trimoxazole [Sulfamethoxazole (SMZ) & Trimethoprim (TM)] is a 2nd-line agent
• Duration of therapy: 3 days except for Azithromycin, Doxycycline, & Ciprofloxacin which are all taken as single doses

Bloody Diarrhea

• Treat the mild dehydration w/ ORT
• Antipropulsives should be avoided as these drugs may increase the severity by delaying excretion of organisms & facilitating invasion of the mucosa
• Once EHEC or Shiga toxin-producing E coli (STEC) has been excluded by stool exam, empiric therapy w/ antibiotics can be started
• Antibiotics following the local sensitivities for Shigella sp may be used as empiric therapy while waiting for culture & sensitivity results
• If local sensitivities are not known, one of the following empiric antibiotics may be used: Ciprofloxacin (drug of choice), 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 w/ empiric & specific antibiotics may be given in certain situations:

Severe cholera & shigellosis
Dysenteric form of campylobacteriosis & 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
• Duration of therapy: 3 days

Campylobacter sp

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

E coli 0157:H7 (enterohemorrhagic, EHEC)

• Avoid antipropulsives & 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 [Sulfamethoxazole (SMZ) & Trimethoprim (TM)], Azithromycin
• Duration of therapy: 5-7 days
• Ceftriaxone may be considered in suspected septicemic cases
• Co-trimoxazole should only be used if organism is susceptible

Shigella sp

• First-line agents: Quinolones
• Second-line agents: Azithromycin, Co-trimoxazole [Sulfamethoxazole (SMZ) & Trimethoprim (TM)], Nalidixic acid, Pivmecillinam, Ceftriaxone
• Duration of therapy: 3 days except for Azithromycin, Nalidixic acid, Pivmecillinam, & Ceftriaxone which are for 5 days

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 agents: Doxycycline plus Tobramycin or Gentamicin
• Second-line agent: Co-trimoxazole [Sulfamethoxazole (SMZ) & Trimethoprim (TM)]

Prevention

Traveler’s Diarrhea

Traveler should avoid:

• Undercooked food except peeled fruits or vegetables
• Non-bottled beverages & unpasteurized dairy products

Bismuth Preparations

• May have protective efficacy over a 7-day period

Probiotics

• May decrease the incidence of diarrhea in travelers
• May have some value in the prevention of antibiotic-associated diarrhea

Cholera

• V cholera is spread through contaminated food & water
• Water can be treated w/ chlorine or iodine, by filtration, or by boiling

Consultation or hospitalization is considered in the following cases:

• Bloody stools
• Frequent & large-volume diarrhea
• Persistent fever & vomiting
• Severe dehydration
• Altered consciousness
• Absence of improvement w/in 48 hr
• No urine output in preceding 12 hr
• Elderly patients
• Presence of chronic medical or concurrent illness