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ACUTE Dr. Solante
ACUTE
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OUTLINE

I.

Diarrhea: Definition

a.

Pathophysiology of Infectious Diarrhea

b.

High-risk Groups

c.

Three types of Enteric Infection

d.

Clinical Features of Infectious Agents

e.

Other causes of Acute Diarrhea

II.

Approach to a patient with diarrhea

a.

Assessment

b.

Stool Laboratory Examination

III.

Diagnostic Tests

IV.

Preventive Measures

a.

Food and Beverage selection

b.

Non-antimicrobial drugs for Prophylaxis

c.

Prophylactic antibiotics

d.

Vaccines

V.

Treatment

 

a.

Antibiotics

b.

Anti-motility agents

c.

Oral rehydration therapy

Appendix: TABLE: Types if Diarrheal Infection

DIARRHEA: Definition

Definition: Passage of abnormally liquid or unformed stools, with increased frequency (if you are going to quantify the frequency it should be more than once) Stool weight > 200 g/day Acute < 2 weeks (vs. Chronic >4 weeks) A commonality in patients with infectious diarrhea is that it is usually a result of the imbalance between the host and the microorganism. The microorganism has the capacity to overwhelm both of the host’s mucosal and non-mucosal defenses. The most important aspect that dictates the severity of the clinical manifestations is the volume of the inoculum of the microorganism in the water or food. (The larger the volume, the more severe the manifestations.) The immune defenses and the virulence of the microorganism have a smaller role in dictating the severity of the manifestations.

Acute Diarrhea: Infectious Diarrhea

More

than

90%

of

acute

diarrhea

are

caused by

infectious agents; often accompanied by vomiting, fever and abdominal pain. The remaining 10% or so are

caused by medications, toxic ingestion, ischemia, and other conditions [Harrison’s]

Infection occurs when the ingested agent overwhelms the host’s mucosal immune and non- immune defenses such as:

o

Gastric acid

o

Digestive enzymes

o

Mucus secretion

o Peristalsis Suppressive resident flora

o

The different pathophysiologic alterations in patients with diarrhea:

  • 1. Altered normal intestinal physiology o Shift in the delicate balance (imbalance) of

the bidirectional water and electrolyte fluxes

in the upper

small bowel by intraluminal

toxins or minimally invasive organisms.

o

Exemplified

by

Giardia

lamblia,

Cryptosporidium which are protozoans

  • 2. Inflammation at the site of infection or cytotoxic destruction of the ileal or colonic mucosa

o

The cells within the mucosa will be destroyed

o

because of the inflammatory reaction caused by the microorganism Destruction may be due to toxins, or the organism itself

  • 3. Direct penetration of the microorganism through an intact mucosa to the reticuloendothelial system

High-risk Groups

Travelers As a traveler sometimes

o

you do

not know the

source of water and the hygienic nature of the food you are eating.

o

Traveler’s diarrhea - most commonly due to E. coli, and also Campylobacter, Shigella, Aeromonas, Coronavirus, Salmonella

Consumers of certain foods

o

These are the individuals who love to eat outside, like students.

o

[Harrison’s]

Vibrio

species,

Salmonella,

or

acute

o

Hepatitis A from seafood, especially if raw Fried rice - Bacillus cereus

o

Eggs - Salmonella

o

Undercooked hamburger – Enterohemorrhagic E.coli

(0157:H7)

o

Mayonnaise, Creams – S. aureus, Salmonella

 

Immunodeficient persons

or

immunocompromised

o

[Harrison’s] Persons with primary immunodeficiency –

IgA

immunodeficiency,

common

variable

hypogammaglobulinemia,

chronic

granulomatous

disease

Daycare attendees and family members

o

Shigella, Giardia, Cryptosporidium, and rotavirus are very common.

Institutionalized persons

o

Infectious diarrhea

one

of

the

most frequent

o

nosocomial infections in many hospitals and long-term care facilities Most commonly caused by Clostridium difficile

Three types of enteric infection

(See APPENDIX for the table)

TYPE 1: Non-inflammatory type

Brought about by

the

toxins

produced by the

microorganisms like Vibrio cholera, E.coli,

C.

perfringens, Bacillus aureus, Staphylococcus aureus Giardia lamblia, Rotavirus, Norwalk-like virus do not produce enterotoxins but they adhere to the tissue and cause superficial invasion. Most of these patients present with watery diarrhea

When you do stool examination, there is absence of leukocytes

Patients

in

this

group

are

prone

to

dehydration

because the diarrhea here involves the proximal

ACUTE Dr. Solante small bowel which is responsible for water absorption systemic infections including viral hepatitis,
ACUTE
Dr. Solante
small bowel which is responsible for water absorption
systemic infections including viral hepatitis, listeriosis,
legionellosis, and toxic shock syndrome

TYPE 2: Inflammatory type

The common pathology is direct invasion and the production of cytotoxins. Most of these microorganisms are lodged in the colon that is why the stool exam of most patients with this type of diarrhea present with abundant leukocytes Examples:

Shigella E. coli (Enteroinvasive, Enterohemorrhagic) Vibrio parahemolyticus (causes bloody diarrhea) Salmonella entiritidis (not all Salmonella are inflammatory) Clostridium difficile Campylobacter jejuni E. histolytica (endemic in the Philippines; does not produce enterotoxins but alters the mucosa which allows invasion of the intestinal mucosa) Characteristics of stool exam: presence of both red blood cells and white blood cells compared to the non-inflammatory

TYPE 3: Penetrating type

Not very common but is very virulent

Salmonella

typhi,

Yersinia

enterocolitica,

Campylobacter fetus These are differential when the patient presents with enteric fever (fever, less of the diarrhea and more of the abdominal cramps, leukocytes in stool examination)

Clinical Features of Infectious Agents [Harrison’s]

Ingestion of preformed bacterial toxins, enterotoxin producing bacteria, and enteroadherent pathogens

o

Profuse

watery

diarrhea

secondary

to

small bowel

o

hypersecretion Diarrhea associated with marked vomiting and minimal or

no fever may occur abruptly within

a

few

hours

after

ingestion of preformed bacterial toxins and enterotoxin

o

producing bacteria Fever is higher in enteroadherent pathogens

 

Invasive bacteria and entamoeba histolytica often causes bloody diarrhea Yersinia invades the terminal ileal and proximal colon mucosa and may cause especially severe abdominal pain with tenderness mimicking acute appendicitis Infectious diarrhea may be associated with systemic manifestations:

o

Reiter’s syndrome (arthritis, urethritis, and conjuctivitis)

o

may accompany or follow infections by Salmonella, Campylobacter, Shigella, and Yersinia Yersiniosis may also lead to an autoimmune-type

o

thyroiditis, pericarditis, and glomerulonephritis Both enterohemorrhagic E.coli (0157:H7) and Shigella can

o

lead to the hemolytic-uremic syndrome The syndrome of postinfectious Inflammatory Bowel

o

Syndrome has now been recognized as a complication of infectious diarrhea Acute diarrhea can also be a major symptom of several

Other Causes of Acute Diarrhea

Medications

o

Side effect of medications is the most common

o

noninfectious cause of acute diarrhea Antibiotics, cardiac antidysrhythmics, antihypertensives, NSAIDs, certain antidepressants, chemotherapeutic agents, bronchodilators, antacids, laxatives

Occlusive or non-occlusive ischemic colitis Typically in persons >50 years old or the elderly

o

with thrombosis in the large intestine which can cause colitis or ischemic colitis

o

Often presents as acute lower abdominal pain preceding watery, then bloody diarrhea

Diverticulitis Graft-versus-host disease (GVHD) or those who are immunocompromised because of mucosal barrier injury brought about by immunosuppressive drugs Acute diarrhea, often associated with systemic compromise can follow ingestion of toxins including:

o

Ingestion of organophosphate insecticides, amanita, other mushrooms, arsenic

o

Preformed

environmental

toxins

in seafood such as

ciguatera and scombroid

APPROACH TO A PATIENT WITH DIARRHEA

ACUTE Dr. Solante small bowel which is responsible for water absorption systemic infections including viral hepatitis,

The most important aspect in the management of patients with diarrhea is to first delineate if it is infectious or non-infectious because each entity entails separate interventions. Example: in an infectious diarrhea you should give an antimicrobial. For a non- infectious etiology you just have to withdraw the cause like a medication, or you can improve the patient’s immune system.

Assessment
Assessment
ACUTE Dr. Solante
ACUTE
Dr. Solante
ACUTE Dr. Solante  The table above is very important. We should emphasize the importance of

The table above is very important. We should emphasize the importance of stool examination in a patient with diarrhea. First, you assess the presence of diarrhea. Most of the time when you have a patient with diarrhea, the most important management is to give symptomatic therapy. Usually it entails the use of oral rehydration therapy. You also have to assess the duration of the diarrhea, severity if it includes signs of dehydration, fever, weight loss, and presence of blood in the stool. If these are present, you have to explore more on the history for you to be able to delineate the etiology. Was there intake of seafood? Antimicrobials? Sexual experience (E. coli in anal sex)? Do a stool examination:

o WBC count: Absence may mean a non- inflammatory type of diarrhea. Presence may mean an inflammatory type of diarrhea and is usually associated with continued systemic illness and for this your differentials are Shigella and Salmonella. Wet mount: look for presence of microorganisms like Giardia and Cryptosporidium.

o

AGAIN:

  • 1. Provide initial assessment and treatment

Rehydration if indicated

Treatment

of

symptoms

with

bismuth

subsalicylate or loperamide if diarrhea is not

inflammatory or bloody If it is non-inflammatory, meaning there

is

absence of WBC in the stool then you can give Loperamide. But if there are WBC then treat accordingly, with an antimicrobial or an anti protozoal because Loperamide is contraindicated in these patients.

2.

Manage subsequently according to clinical findings and epidemiology.

Clinical findings: fever, severe and/or bloody diarrhea, abdominal pain

Epidemiology: travel, food and water exposure, adventure travel, season

3.

Stool laboratory exams if diarrhea is severe, bloody, or persistent.

Indications for evaluation [Harrison’s]

Profuse diarrhea with dehydration

Grossly bloody stools

Fever >/= 38.5 C

Duration > 48 hours without improvement

Recent antibiotic use

New community outbreaks

Associated severe abdominal pain in patients >50 years

old Elderly (>/=70 years old)

Immunocompromised patients

Stool Laboratory Examination

ACUTE Dr. Solante  The table above is very important. We should emphasize the importance of

For Traveler’s diarrhea you just have to identify the common etiology. For example, if diarrhea is less than

ACUTE Dr. Solante
ACUTE
Dr. Solante

7 days

then

the

possible

etiologic

agents

are

Salmonella, Shigella and Campylobacter. You then do stool culture to identify which of these 3 is the

pathogen. Do Shiga toxin assay for E. coli 0157:H7 if

there is bloody

stool. If there

is history

of

seafood

intake then culture for Vibrio.

For diarrhea after antimicrobial therapy (like beta lactams, ampicillin, amoxicillin, co-trimoxazole) the common etiologic agent is C. difficile. Do an assay using blood to identify the presence of the C.difficile toxins A and B.

For

persistent

diarrhea,

there

is

commonly the

presence

of ova and parasites.

Do

a

wet mount for

antigen detection.

DIAGNOSTIC TESTS

There are specific staining methods for you to identify specific microorganisms:

PROCEDURE

 

PURPOSE

 

Microscopy of fresh unstained wet prep of stool

Detection of live actively motile protozoan trophozoites (E. histolytica, Giardia) and helminth larvae (Strongyloides), Helminth eggs and RBCs, WBCs also

 

observed

WBCs by microscopy, use of Methylene blue or presence of lactoferrin

 

Many WBCs suggests bacterial infection

 

Microscopy of concentrated sediment

Detection of helminth eggs and larvae,

of preserved stool

protozoan cysts

 

Microscopy of trichrome-stained fecal smear

Detection of protozoan cysts, trophozoites

Microscopy w/ special stains (modified Kinyoun/afb, trichrome blue, safranin)

Detection of Cryptosporidium, microsporidia, Cyclospora

Fecal antigen detection by EIA or fluorescent

Specific identification for Giardia, Cryptosporidium,

antibody

E. histolytica

Bacterial

culture

of

Detection

of

enteric

stool

pathogens

The most common is microscopy of fresh unstained wet preparation of stool. It is very important in the identification of protozoan eggs or cysts.

PREVENTIVE MEASURES

Food and Beverage selection

o Eat only freshly cooked foods, served hot o Avoid beverages diluted in non-potable water

Reconstituted fruit juice

Ice

Milk o Avoid food washed in non-potable water

o Avoid risky foods: raw, undercooked meat, seafood, unpeeled raw fruits and vegetables o Drink safe beverages

Bottled, sealed, carbonated

Boiled or treated with iodine or chlorine

o Restaurant hygiene?

Non-antimicrobial drugs for prophylaxis

Bismuth subsalicylate (BSS)

o

Anti-diarrheal (non-bloody, inflammatory)

non-mucosal,

non-

o

Reduces incidence of traveler’s diarrhea from 40%

o

to 14% Taken as either 2 oz. of liquid or 2 chewable tablets

4x/day

o

Adverse reactions: nausea, vomiting, blackening of

tongue and stool, constipation, tinnitus

 

o

Contraindications:

aspirin

allergy,

renal

o

insufficiency, gout Drug interactions: Probenecid, anticoagulants,

antiplatelets, Methotrexate

Probiotics (Lactobacillus spp., Saccharomycesboulardii)

o

Inconclusive results as to its benefits

o

Purpose is to enhance the growth of good bacteria

o

Not highly recommended

o

Yogurt, Yakult, etc.

Bovine colostrum

o

Enhance the growth of colonizers (Lactobacillus)

o

Commercially available preparations not FDA-

approved

o

No data from rigorous clinical trials that it is highly

beneficial

Prophylactic Antibiotics

NOT RECOMMENDED; Antibacterial prophylaxis is not recommended in infectious diseases No protection against non-bacterial pathogens

We

do

not

know

if

there are

allergic or adverse

reactions if these are given. Use should be weighed against result of using prompt,

early treatment

[Harrison’s] Antibiotic prophylaxis is indicated for certain

patients traveling to high-risk countries in whom the likelihood or seriousness of acquired diarrhea would be especially high, including those with immunocompromise, inflammatory bowel disease, or gastric achlorhydria. Use of trimethoprim/sulfamethoxazole or ciprofloxacin may reduce bacterial diarrhea such travelers by 90%.

Vaccines
Vaccines

Cholera, Rotavirus, HAV

The

best

intervention

Philippines)

(including

travel

to

the

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TREATMENT Antibiotics
TREATMENT
Antibiotics

Should be given as a treatment and not as prophylaxis. Given to inflammatory and penetrating types of diarrhea to decrease toxin production and tissue invasion. Non-inflammatory diarrhea is usually self- limiting and only rehydration is needed. Fluoroquinolones: Treatment of moderately to severely ill patients with febrile dysentery without diagnostic evaluation e.g. Ciprofloxacin (500 mg bid for 3-5days) Azithromycin Rifaximin

o

Overall usefulness has to be determined

Metronidazole, Tinidazole, Nitazoxanide Metronidazole – for suspected Entamoeba histolytica, giardiasis (250 mg qid for 7 days)

Antimotility agents

Should be given together with antimicrobials

Symptomatic relief as it decreases peristalsis of small and large bowel. But this may not be enough as the transit time for excretion of the microorganism is also decreased, that is why you have to give antibiotics at the same time. Adjuncts in moderately severe, nonfebrile, nonbloody diarrhea (Loperamide) Synthetic opiates – Loperamide, Diphenoxylate

o

Reduce bowel movement frequency

o

Antisecretory properties (Loperamide)

Should be avoided with febrile dysentery, which may be exacerbated or prolonged

Oral Rehydration Therapy

Mainstay, cheapest form Fluid replacement alone may suffice for mild diarrhea:

Beneficial in patients with non-inflammatory type of diarrhea who are prone to dehydration. The most common derangement in dehydrated patients is electrolyte imbalance (usually hyponatremia and hypokalemia). Relatively unpalatable (salty) Oral sugar-electrolyte solutions (sports drinks, designed formulations) should be instituted promptly with severe diarrhea to limit dehydration Profoundly dehydrated patients require IV rehydration

especially infants and the elderly

Add

1

packet to

treated water

appropriate volume of boiled or

ACUTE Dr. Solante Composition of WHO Oral Rehydration Salts for Diarrheal illness
ACUTE
Dr. Solante
Composition
of
WHO
Oral
Rehydration
Salts
for
Diarrheal
illness
ACUTE Dr. Solante Ingredient Amount Sodium Chloride 2.6 g/L Potassium Chloride Glucose anhydrous 1.5 g/L 13.5
ACUTE
Dr. Solante
Ingredient
Amount
Sodium Chloride
2.6 g/L
Potassium Chloride
Glucose anhydrous
1.5 g/L
13.5 g/L
Trisodium
citrate,
2.9
g/L
(or
2.5
dehydrate
g/L)
Water
1 L
ACUTE Dr. Solante Ingredient Amount Sodium Chloride 2.6 g/L Potassium Chloride Glucose anhydrous 1.5 g/L 13.5

1.

5.

A

SAMPLE QUESTIONS

55 year old male with diabetes was admitted because of

  • 2. the following

Which of

organism produces diarrhea by

respiratory tract infection. A few days after antibiotics were

producing toxins?

started, patient developed abdominal pain, with fever,

  • a. Bacillus cereus

vomiting and bloody diarrhea. Most probable cause of the

  • b. Rotavirus

patient’s bloody diarrhea is

  • c. Giardia

  • a. Salmonella typhi

  • d. Clostridium difficile

  • b. Shigella sp

  • c. Clostridium difficile

  • 3. Which of the following is an indicator for further work up in a patient with diarrhea?

  • d. E. histolytica

  • a. Duration >24 hours with improvement of symptoms

  • 6. Diagnostic test that would confirm the diagnosis of the

  • b. Elderly >70 years old

above patient would be

  • c. Patients with low grade fever

  • a. Blood culture

  • d. Watery, mucoid stools

  • b. Stool exam

  • c. C. difficile toxin assay

  • 4. Antibiotic prophylaxis is recommended for the following patients travelling to high risk countries

  • d. Colonoscopy

  • a. Elderly

  • 7. Treatment for the above patient would be

  • b. Patients with mechanical heart valves

  • a. Ciprofloxacin

  • c. Patients with gastric achlorhydria

  • b. Ceftriaxone

  • d. Patients with recent vascular graft

  • c. Amoxicillin

ACUTE Dr. Solante d. Metronidazole
ACUTE
Dr. Solante
d.
Metronidazole
  • 8. A 35 year old missionary from Australia developed

10. A 20 year old male patient developed diarrhea occurring >10x per day amounting to >1L/episode. Stools were

  • a. Vibrio cholera

abdominal pain with 2-3 episodes of bloody diarrhea for 2 days after arrival to the Philippines. Patient has no signs of dehydration on examination. Most likely etiology of

characterized as rice-water appearance. Most likely etiology of diarrhea is

patient’s symptoms is

  • b. Salmonella infection

  • a. Rotavirus

  • c. Entamoeba histolytica

  • b. Escherichia coli

  • d. Bacillus cereus

  • c. Entamoeba coli

  • d. Helminthes

11. A 30 year old businessman developed watery stools,

  • 9. Aside from hydration, management for the above patient would include

    • a. Viral culture

    • b. Antibiotics

    • c. Admit patient for observation

    • d. Urgent colonoscopy

<6x/day, with low grade fever and mild abdominal pain of 3 days duration. No signs of dehydration noted. Most likely etiology of diarrhea is

  • a. Rotavirus

  • b. Shigella infection

  • c. Entamoeba histolytica

d.

EHEC