Gi 12: Infectious Diarrhea

Front 1

What is the second leading cause of morbidity and mortality worldwide?

Back 1

Infectious diarrheal disease

Front 2

What is the leading cause of childhood death worldwide?

Back 2

Infectious diarrheal disease

Front 3

What is the typical course of diarrhea?

Back 3

Most are self-limited

Front 4

What is the most common symptom of food borne illness in the US? How many cases per year? Hospitalizations/deaths?

Back 4

- Most have diarrhea
- 76 million illnesses
- 325,000 hospitalizations
- 5000 deaths

Front 5

How common are diarrheal illnesses in the US/year? Hospitalizations?

Back 5

- 211-375 million episodes
- 1.8 million hospitalizations

Front 6

How long can an ACUTE case of diarrhea be? PERSISTENT?

Back 6

- Acute: ≤ 14 days
- Persistent: > 14 days

Front 7

What is the definition of diarrhea?

Back 7

- >200g / 24 hour period (not clinically useful)

- 3 or more loose/watery stools per day
- OR a clear increase in frequency and decrease in consistency over baseline

Front 8

How often does a patient have a BM in diarrhea? Volume?

Back 8

- 3-7 BM/day (up to 20 BM/day)
- Volume < 1000cc/day

Front 9

When do most cases of diarrhea occur?

Back 9

Winter months (viral)

Front 10

How long is the small intestine?

Back 10

3 to 8 meters (average 6m)

Front 11

What macronutrients are absorbed in the small intestine? Where?

Back 11

- Carbs, fats, and nitrogen
- Absorbed in proximal 100-150 cm

Front 12

How much volume is absorbed in the small intestine?

Back 12

10L in and 1.5L out (total absorbed: 8.5 L)

Front 13

How much volume is absorbed in the large intestine?

Back 13

1.5L in and 0.1L out (total absorbed: 1.4L)

Front 14

How much volume is usually excreted out of the anus?

Back 14

0.1 L
(diarrhea > 0.2L)

Front 15

What are the symptoms of an infection in the small bowel?

Back 15

- Water diarrhea, large volume
- Abdominal cramping, bloating, gas, and weight loss
- Fever RARE
- Rare stool WBCs or occult blood

Front 16

What are the symptoms of an infection in the large bowel?

Back 16

- Frequent, small, regular stools
- Painful BM or tenesmus (a continual or recurrent inclination to evacuate the bowel)
- Fever, bloody, mucoid stools
- RBCs and WBC on stool smear

Front 17

What are the most common causes of infection to the colon?

Back 17

- Most gastroenteritis is viral (cultures only positive in 1.5-5.6%)

- Severe community acquired diarrhea (87% bacteria)

Front 18

What is the definition of severe community acquired diarrhea?

Back 18

– defined as ≥4 fluid stools per day
– > three days
– 87% bacterial

Front 19

What are the most common viral pathogens in the intestines?

Back 19

Small:
- Rotovirus
- Norwalk

Large:
- CMV
- Adenovirus
- Herpes simplex virus

Front 20

What are the most common protozoan pathogens in the intestines?

Back 20

Small:
- Cryptosporidium
- Microsporidium
- Isospora
- Cyclospora
- Giardia lamblia

Large:
- Entamoeba histolytica

Front 21

What are the non-infectious causes of diarrhea?

Back 21

• Drugs – antibiotics, laxative abuse
• Food allergies
• IBD, IBS
• Thyrotoxicosis
• Carcinoid/Neuroendocrine tumors
• Ischemic colitis
• Stool impaction – overflow diarrhea
• Stress

Front 22

What happens in "osmotic diarrhea"?

Back 22

Neither the small intestine nor the colon can maintain an osmotic gradient

Unabsorbed ions that remain in the lumen
– Retain water
– Maintain an intraluminal osmolality = 290 mOsm/kg

Front 23

What can cause "osmotic diarrhea"?

Back 23

Ingestion of poorly absorbed ions or sugars or sugar alcohols
– Mannitol, sorbitol
– Magnesium, sulfate, and phosphate

Monosaccharides—but not disaccharides—can be absorbed intact across the apical membrane of the intestine
– Disaccharidase (lactase) deficiency will prevent absorption
– “lactose intolerance”

Front 24

What fixes osmotic diarrhea?

Back 24

• Disappears with fasting
• Or cessation of the offending substance

Front 25

What happens to electrolytes in osmotic diarrhea?

Back 25

• Electrolyte absorption is not impaired in osmotic diarrhea
• Electrolyte concentrations in stool water are usually quite low

Front 26

What happens in "secretory diarrhea"?

Back 26

– Either net secretion of anions (chloride or bicarbonate)
– Or inhibition of net sodium absorption

Front 27

What are the causes of Secretory Diarrhea?

Back 27

• The most common cause is infection

• Enterotoxins
– Interact with receptors and modulate intestinal transport
– Block specific absorptive pathways, in addition to stimulating secretion.
– Inhibit Na+-H+ exchange in both the small intestine and colon

• Peptides produced by endocrine tumors

Front 28

What kind of diarrhea is caused by Enterotoxins? Mechanism?

Back 28

Secretory Diarrhea:
– Enterotoxin interacts with receptors and modulates intestinal transport
– Blocks specific absorptive pathways, in addition to stimulating secretion
– Inhibits Na+-H+ exchange in both the small intestine and colon

Front 29

What is the osmolality of colonic fluid contents?

Back 29

Usually in equilibrium with body fluids (290 mOsm/kg)

Front 30

How do you calculate the Osmotic Gap?

Back 30

Osmotic Gap = Serum Osm – Estimated stool Osm

Estimated stool Osm = (2 × ([Na+] + [K+]))
Serum Osm = ~290 mmol/L

Front 31

What happens to electrolytes in Secretory Diarrhea? Osmotic gap?

Back 31

In secretory diarrhea, almost all of the osmotic activity of stool is accounted for by electrolytes
– Therefore, (2 × ([Na+] + [K+])) ~ 290 mmol/L.
– Small osmotic gap (<50 mOsm/kg)

Front 32

What happens to electrolytes in Osmotic Diarrhea? Osmotic gap?

Back 32

– Electrolytes only a small part of the osmotic activity
– Unmeasured osmoles account for most of the osmotic activity
– The calculated osmotic gap will be high.
– Osmotic gap is present (>100 mOsm/kg)

Front 33

What does it mean if the osmotic gap is negative?

Back 33

Poorly absorbed multivalent anion such as phosphate or sulfate

Front 34

What happens to the stool osmolality once stool is collected? What does this indicate about the value of this measurement?

Back 34

- Tends to rise once stool is collected because of continuing bacterial fermentation in vitro
- Therefore, measured stool osmolality is of little value

Front 35

How can you evaluate if your patient is using laxatives surreptitiously (in secret)?

Back 35

• Stool water can be analyzed for laxatives by chemical or chromatographic methods
• Large osmotic gap suggests magnesium ingestion

Front 36

When would a stool osmolarity test be useful?

Back 36

- Surreptitious (secretive) laxative ingestion
- Very high if diluted with urine
- Very low if diluted with water

Front 37

What are the common bacterial infectious causes of diarrhea?

Back 37

- Salmonella typhi
- Shigella
- Campylobacter jejuni
- Escherichia coli
- Enterohemorrhagic E. coli (EHEC)
- Vibrio cholerae

Front 38

What is the #1 foodborne disease in US? How common?

Back 38

Salmonella typhi (36%)

Front 39

What kind of bacteria is Salmonella typhi? What foods is it associated with?

Back 39

- G- encapsulated bacilli
- Found in poultry, eggs, and milk

Front 40

Besides food, what else is associated with Salmonella typhi infections?

Back 40

Pet turtles

Front 41

What are the risk factors for infection of Salmonella typhi?

Back 41

- Summer and fall
- Young age
- IBD
- Immune deficiencies

Front 42

What kind of illness is caused by Salmonella typhi?

Back 42

- Colonic or dysenteric like disease
- Although small bowel disease
- Typhoid fever

Front 43

What organ can be affected by Salmonella typhi in Typhoid Fever? Results?

Back 43

- Gallbladder can be colonized
- May be associated with gallstones and a chronic carrier state

Front 44

What are the signs of an acute infection of Salmonella typhi in Typhoid Fever?

Back 44

- Anorexia
- Abdominal pain
- Bloating
- Nausea
- Vomiting
- Bloody diarrhea

Front 45

What can happen int he second phase of infection with Salmonella typhi in Typhoid Fever?

Back 45

Can develop bacteremia with associated fever

Front 46

What disease causes patients to be susceptible to Salmonella typhi infection? How are they affected?

Back 46

Patients with sickle cell disease are particularly susceptible to Salmonella osteomyelitis

Front 47

What is the cause of ~10% of pediatric diarrheal disease and 75% of diarrheal deaths?

Back 47

Shigella

Front 48

What kind of bacteria is Shigella? How is it spread?

Back 48

- G- bacillli
- Unencapsulated
- Facultative anaerobe

- Spread via fecal-oral route, highly contagious (small inoculum required ~10-100 organisms and acid resistant)

Front 49

What is associated with Shigella infection?

Back 49

Daycare and institutional settings, can be transmitted person to person (fecal oral)

Front 50

What kind of disease is caused by Shigella infection? Symptoms?

Back 50

- Self-limited
- ~6 days of diarrhea, fever, and abdominal pain

Front 51

Which part of the GI tract is affected by Shigella?

Back 51

Left colon, but ileum may also be involved (can mimic Crohn's disease)

Front 52

How can you shorten the clinical course (~6 days) of Shigella infection? How should you not treat?

Back 52

* Treat with Antibiotics

- Avoid anti-diarrhea meds (delays bacterial clearance)

Front 53

What can rarely occur with Shigella infection?

Back 53

- Hemolytic Uremic Syndrome
- Seizures
- Reactive arthritis

Front 54

What is the leading cause of acute bacterial diarrhea worldwide?

Back 54

Campylobacter jejuni (33% of foodborne illness)

Front 55

How is Campylobacter jejuni obtained?

Back 55

- Undercooked poultry
- Unpasteurized milk
- Contaminated water
- Requires ingestion of only 500 C. jejuni organisms

Front 56

How long does Campylobacter jejuni incubate? What are the symptoms?

Back 56

- Incubates up to 8 days
- Usually influenza like prodrome (early on)
- Dysentery (severe diarrhea with the presence of blood and mucus in the feces) develops in 15-50%
- Watery or hemorrhagic, both small and large intestinal symptoms

Front 57

How do you treat Campylobacter jejuni?

Back 57

Usually it is self-limited so antibiotics are not required

Front 58

*What can Campylobacter jejuni result in / associated with?

Back 58

- REACTIVE ARTHRITIS or erythema nodosum
- GUILLAIN-BARRÉ SYNDROME
- PSEUDOAPPENDICITIS (very bad abdominal pain)

Front 59

Which bacterial infection is associated with Reactive Arthritis or Erythema Nodosum?

Back 59

Campylobacter jejuni

Front 60

Which bacterial infection is associated with Guillain-Barré Syndrome

Back 60

Campylobacter jejuni
- Flaccid paralysis caused by auto-immune induced inflammation of peripheral nerves

Front 61

Which bacterial infection can cause abdominal pain typically worse than others "pseudoappendicitis"?

Back 61

Campylobacter jejuni

Front 62

What is the most common pathogenic parasitic infection in humans?

Back 62

Giardia lamblia

Front 63

What kind of parasite is Giardia lamblia? How is it spread?

Back 63

Flagellated protozoan - spread through fecally contaminated water or food

Front 64

Where is Giardia lamblia commonly obtained?

Back 64

Endemic in unfiltered public and rural water supplies ("drinking from mountains streams") - caused by fecally contaminated water or food

Front 65

25 y/o male returns from a 10 day backpacking trip in Rocky Mountain National Park. He develops upper abdominal bloating and cramping with watery diarrhea. What is the MOST LIKELY cause of his symptoms?
a) Enterotoxigenic E. coli
b) Enterohemorrhagic E. coli
c) Giardia Lambia
d) Norovirus
e) Hookworm infection

Back 65

Giardia Lamblia

Endemic in unfiltered public and rural water supplies ("drinking from mountains streams") - caused by fecally contaminated water or food

Front 66

What are the symptoms of Giardia Lamblia infection?

Back 66

- Acute or chronic diarrhea w/ upper abdominal bloating
- Small bowel disease

Front 67

What kind of bacteria is Escherichia coli? Where does it colonize?

Back 67

G- bacilli - colonizes the healthy GI tract

Front 68

What is the principal cause of TRAVELER'S DIARRHEA?

Back 68

Enterotoxigenic E. coli (ETEC) organisms

Front 69

How is Enterotoxigenic E. coli (ETEC) obtained?

Back 69

Fecal-oral route (most common cause of traveler's diarrhea)

Front 70

What does Enterotoxigenic E. coli (ETEC) express? Implications?

Back 70

- Heat labile toxin (LT) that is similar to cholera toxin (increases cAMP)
- Heat stable toxin (ST) that increases intracellular cGMP w/ effects similar to cAMP elevations caused by LT

Front 71

Which toxin increases cAMP and is similar to cholera toxin?

Back 71

Heat labile toxin (LT) from Enterotoxigenic E. coli (ETEC) organisms

Front 72

Which toxin increases intracellular cGMP?

Back 72

Heat stable toxin (ST) from Enterotoxigenic E. coli (ETEC) organisms

Front 73

Which organism resembles Shigella but does not produce toxins?

Back 73

Enteroinvasive E. coli (EIEC) organisms

Front 74

What is the pathogenesis of Enteroinvasive E. coli (EIEC) organisms?

Back 74

- Resembles Shigella but does not produce toxins
- Invades gut epithelial cells
- Produces a bloody diarrhea

Front 75

Which organism attaches to enterocytes by adherence fimbriae?

Back 75

Enteroaggregative E. coli (EAEC) organisms

Front 76

What is the pathogenesis of Enteroaggregative E. coli (EAEC) organisms?

Back 76

– Attach to enterocytes by adherence fimbriae.
– Although they produce LT and Shiga-like toxins, histologic damage is minimal

Front 77

What type of E. coli is also known as 0157:H7?

Back 77

Enterohemorrhagic E.Coli (EHEC)

Front 78

How is Enterohemorrhagic E.Coli (EHEC) spread? How common?

Back 78

- Undercooked beef
- Mishandling of ground beef
- 4% of foodborne illness
- 39% of cultured pathogens in visibly bloody specimens

Front 79

What is Enterohemorrhagic E.Coli (EHEC) associated with?

Back 79

Hemolytic Uremic Syndrome (hemolysis and renal failure)

Front 80

How should you treat Enterohemorrhagic E.Coli (EHEC)?

Back 80

Not with antibiotics - this can potentially make it worse

Front 81

What kind of organism is Vibrio cholerae? How is it spread?

Back 81

G- bacteria, non-invasive
- Spread in contaminated drinking water
- Associated w/ seafood: shellfish and plankton

Front 82

What kind of toxins are released by Vibrio cholerae? Mechanism of action?

Back 82

Enterotoxin, cholera toxin → disease:
- Increases intracellular cAMP →
- Opens the cystic fibrosis transmembrane conductance regulator (CFTR) →
- Releases Cl- ions into lumen
- Draws water into lumen

Front 83

What are the symptoms of infection by Vibrio cholerae? Incubation period?

Back 83

- Most are asymptomatic or suffer only mild diarrhea

- Severe disease: abrupt onset of watery diarrhea and vomiting
- May reach 1L/hr → dehydration, hypotension, electrolyte imbalances, anuria, shock, and death

- Incubation period of 1 to 5 days

Front 84

What are the viral causes of infectious diarrhea?

Back 84

- Norovirus
- Rotavirus

Front 85

What is the cause of approximately half of all gastroenteritis outbreaks worldwide?

Back 85

Norovirus

Front 86

What are the most common causes of Norovirus?

Back 86

- Contaminated food or water
- Person-to-person as well
- Schools, hospitals, nursing homes, and most recently cruise ships

Front 87

If you are on a cruise, what is probably the cause of your infectious diarrhea?

Back 87

Norovirus (contaminated food and water or person-to-person)

Front 88

What are the symptoms of Norovirus infection? Time course?

Back 88

- Nausea
- Vomiting
- Watery diarrhea
- Abdominal pain
- Self-limited

Front 89

What is the most common cause of childhood diarrhea and diarrhea-related deaths worldwide? How common?

Back 89

Rotavirus
- Infects 140 million people
- Causes 1 million deaths

Front 90

Who is most vulnerable to Rotavirus infection? Location? How can you prevent?

Back 90

- Children between 6 and 24 months
- Outbreaks in hospitals and day care centers
- Vaccines now available

Front 91

What are the symptoms of Rotavirus infection? Time course?

Back 91

- Vomiting
- Watery diarrhea
- Several days

Front 92

What are the parasitic causes of infectious diarrhea?

Back 92

- Giardia lamblia (protozoa)
- Ascaris lumbricoides and Strongyloides (nematodes)
- Necator americanus and Ancylostoma duodenale (hookworms)

Front 93

What nematode can cause infectious diarrhea? How common? How is it spread?

Back 93

Ascaris lumbricoides
- Infects >1 billion people worldwide
- Spread fecal-oral route
- Can also cause Ascaris pneumonitis

Front 94

What is the life cycle of Ascaris lumbricoides?

Back 94

1. Ingested eggs hatch in the intestine
2. Larvae penetrate the intestinal mucosa
3. Larvae migrate to the liver, creating hepatic abscesses
4.Larvae get into systemic circulation to the lung, where they can cause Ascaris pneumonitis
5. In lung, larvae migrate up the trachea, are swallowed, and arrive again in the intestine to mature into adult worms

Front 95

Where is Strongyloides found? How does it infect patients?

Back 95

- Larvae live in fecally contaminated ground soil
- Larvae can penetrate through unbroken skin

Front 96

What is the lifecycle of Strongyloides?

Back 96

1. Larvae penetrate through unbroken skin
2. Migrate through lungs to trachea from where they are swallowed
3. Mature into adult worms in the intestines
4. Eggs can hatch within intestine and release larvae that penetrate mucosa
5. Causes vicious cycle / auto-infection
6. Persists for life, immunosuppressed individuals can develop overwhelming infections

Front 97

What are the hookworms that can cause infectious diarrhea?

Back 97

- Necator americanus
- Ancylostoma duodenale

Front 98

How common are Necator americanus and Ancylostoma duodenale infections?

Back 98

Infect 1 billion people worldwide

Front 99

What is the Necator americanus and Ancylostoma duodenale life-cycle

Back 99

1. Infection by larval penetration through skin
2. Further develops in lungs
3. Larvae then migrate up trachea and are swallowed
4. Once in duodenum, larvae rupture and adult worms attach to the mucosa, suck blood, and reproduce

Front 100

What is the leading cause of iron deficiency anemia in the developing world?

Back 100

Necator americanus and Ancylostoma duodenale infections (hookworms)

Front 101

What is Necator americanus and Ancylostoma duodenale infection associated with?

Back 101

Iron deficiency anemia

Front 102

What is the definition of Nosocomial Diarrhea (hospital associated)?

Back 102

New diarrhea at least 72 hours after admission

Front 103

What are the implications of Nosocomial Diarrhea (hospital associated)? Who is affected?

Back 103

- Increases length of stay from one week to one month
- Severity and LOS mostly depend on age
- Elderly have increased incidence and mortality

Front 104

What are the causes of Nosocomial Diarrhea (hospital associated)?

Back 104

• Clostridium difficile
• Tube feeds
• Medications
• Fecal impaction
• Ischemic Colitis
• BMT patients – CMV, HSV, GVHD

Front 105

How do you diagnose C. difficile?

Back 105

- Order C. diff toxin only
- Culture is of little value unless there is an outbreak

Front 106

What should be your diagnostic approach to determining the cause of the patient's diarrhea?

Back 106

* History!!
- Past medical, social, occupational, sexual histories
- Duration, characteristics, and frequency
- Assess volume status, fever, and abdominal tenderness
- Rectal exam
- Labs: TSH, BNP, MG, Phos, CBC, Lactate, LFTs

Front 107

Which labs should you do to assess the cause of diarrhea?

Back 107

- TSH
- BNP
- MG
- Phos
- CBC
- Lactate
- LFTs

Front 108

What kind of questions should you ask in your history of a patient to describe the diarrhea?

Back 108

• Try to quantify volume
• Try to assess constancy: loose vs. watery
• Frequency
• Pain, with BM, relieved with BM?
• Wakes at night
• Gas/bloating

Front 109

If a patient has a fever with their diarrhea, what should you be thinking?

Back 109

• Invasive bacteria
• Enteric viruses
• Cytotoxic organism: Clostridium difficile or Entamoeba histolytica
• Ischemia
• IBD

Front 110

What kind of questions should you ask in your history of a patient with describe to try to determine a possible cause?

Back 110

• Recent antibiotic use or chemotherapy
• Family members ill or near outbreaks
• Nursing home residence
• Occupational exposure – health care or day care
• Recent and remote travel
• Pets (dairy farmers)
• Hobbies (drinking from mountain streams).
• Consumption of unpasteurized dairy products, undercooked meat or fish, or organic vitamin preparations

Front 111

What does the timeline of diarrhea in relation to food tell you?

Back 111

- Began within 6 hours: suggests ingestion of a toxin (S. aureus or B. cereus)
- Began 8-14 hours later: suggests infection w/ Clostridium perfringens
- Began more than 14 hours later: suggests viral or bacterial infection, non-specific

Front 112

If diarrhea began within six hours of consuming the infected food, what do you think of as the cause?

Back 112

Suggests ingestion of a toxin:
- S. aureus (potato salad)
- Bacillus cereus (Chinese food / rice)

Front 113

If diarrhea began six to 14 hours after consuming the infected food, what do you think of as the cause?

Back 113

Clostridium perfringens

Front 114

If diarrhea began more than 14 hours after consuming the infected food, what do you think of as the cause?

Back 114

Viral or bacterial infection, but non-specific

Front 115

What tests can be used in a case of infectious colitis? Which are effective / non-effective?

Back 115

- Smear: histologically most bacterial infections look the same
- Culture: effective for determining diagnosis
- Endoscopy: not usually indicated in acute diarrhea

Front 116

What are the characteristics of a stool culture?

Back 116

• Bacterial pathogens generally are excreted continuously
• Negative culture usually not a false negative
• Repeat specimens are rarely required

Front 117

When should you order a stool culture?

Back 117

• Severely ill or requiring hospitalization
• Outbreaks
• Immunocompromised patients, e.g. HIV
• Patients with comorbidities
• Patients with IBD
• Some employees, such as food handlers, may require negative stool cultures to return to work

Front 118

What are the characteristics of a Stool for O and P test (Ova and Parasites)?

Back 118

• Many false negative b/c ova shed intermittently
• Repeated X3
– 3 consecutive days – 24 hours apart.
• Useless in most patients
• Not cost effective

Front 119

When should you order a stool for O and P test (ova and parasites)?

Back 119

• Persistent diarrhea >14 days
• Travel to mountainous regions
• Exposure to infants in daycare centers
• Immune-compromised
• A community water-borne outbreak

Front 120

What can ELISAs or DFA (direct fluorescent antibody) microscopy be used to diagnose? Efficacy?

Back 120

- Giardiasis
- Cryptosporidium in stool
- Sensitivity >90% and specificity approaching 100%

Front 121

What are the mainstays of treating all types of diarrhea?

Back 121

** Hydration **
- Oral rehydration

Front 122

How does the body reabsorb glucose, salt and water?

Back 122

- Intestinal glucose absorption via sodium-glucose cotransport remains intact
- Intestine able to absorb water if glucose and salt are also present (add salt to gatorade)

Front 123

What should the contents of the oral solutions used to rehydrate a patient with diarrhea?

Back 123

- 3.5g NaCl
- 2.9g Trisodium citrate or 2.5g Sodium Bicarbinate
- 1.5g KCl
- 20g glucose or 40g sucrose in 1L of water

Or to 1L of water, add:
- 1/2 tsp salt
- 1/2 tsp baking soda
- 4 tablespoons sugar

- Gatorade not adequate for severely ill patients, but it is likely adequate for otherwise healthy patients

Front 124

What are the symptoms of moderate to severe Travelers' Diarrhea (ETEC)? Treatment? Efficacy?

Back 124

Symptoms:
- >4 stools / day
- Fever
- Blood, pus, or mucus in stool

Treatment is empirical:
- Promptly with Fluoroquinolone or TMP-SMZ
- Can reduce duration from 3-5 to 1-2 days

Front 125

What are the indications for empiric antibiotics? Treatment regimens?

Back 125

Symptoms:
- Fever
- Bloody diarrhea
- Occult blood or fecal leukocytes in stool
- > 8 stools / day

Other indications:
- Volume depletion
- Symptoms > 1 week
- Hospitalized patients
- Immunocompromised hosts

Treatment:
- Fluoroquinolone 3-5 days
- Azithromycin and Erythromycin are alternatives particularly if you suspect Fluoroquinolone resistance

Front 126

What is the first line empiric antibiotic for diarrhea that meets criteria?

Back 126

Fluoroquinolone for 3-5 days

Front 127

What are the alternative agents for empiric treatment of diarrhea that meets criteria?

Back 127

- Azithromycin
- Erythromycin
(used when fluoroquinolone resistance is suspected)

Front 128

What anti-motility agents can be used to treat diarrhea? When can they be used?

Back 128

- Loperamide
- Diphenoxylate

- Only if fever is absent and stools are not bloody

Front 129

What can use of the anti-motility agents, Loperamide and Diphenoxylate, potentially cause?

Back 129

May facilitate the development of Hemolytic Uremic Syndrome in EHEC

Front 130

What kind of bacteria is C. difficile?

Back 130

- G+ spore forming
- Anaerobic

Front 131

What are the risk factors for C. difficile?

Back 131

• Recent Antibiotic Use
• Age
• Duration of Hospital Stay
• Chemotherapy
• Inflammatory Bowel Disease
• AIDS
• GI surgery or G tube?
• Antiacids?

Front 132

How is C. difficile transmitted? Incubation period?

Back 132

- Fecal-oral transmission
- Takes 2-3 days to get symptoms

Front 133

Who gets asymptomatic colonization of C. difficile?

Back 133

- 7-26% of inpatients
- 2% of outpatients (with no recent healthcare exposure)
- Newborns have high carrier rate
- Risk persists for weeks following antibiotic therapy

Front 134

What is the life-cycle of C. difficile infection?

Back 134

1. C. diff spores and vegetative cells ingested
2. Most vegetative cells are killed in the stomach, but the spores can survive the acid environment
3. C. diff spores germinate in small bowel upon exposure to bile acids
4. Flagellae facilitate C. diff movement; a polysaccharide capsule discourages phagocytosis
5. C. diff multiples in the colon
6. Gut mucosa facilitates adherence to colonic epithelium to mediate infection

Front 135

Where do C. difficile spores germinate? What stimulates germination?

Back 135

- In small intestine
- Upon exposure to bile acids

Front 136

What discourages phagocytosis of C. difficile in the intestine?

Back 136

Polysaccharide capsule

Front 137

Where does C. difficile multiply? What happens there?

Back 137

- Multiplies in colon
- Gut mucosa facilitates adherence to colonic epithelium

Front 138

What toxins does C. difficile produce? How do they compare genetically and structurally?

Back 138

- Toxin A and Toxin B
- Genes reside on the same pathogenic locus
- Toxins share similar structural features

Front 139

What are the characteristics of Toxin A from C. difficile?

Back 139

- Gene: TcdA
- Potent enterotoxin (affects the intestines)
- Most non-epidemic strains

Front 140

What are the characteristics of Toxin B from C. difficile?

Back 140

- Gene: TcdB
- Cytotoxin in vitro
- Most non-epidemic strains

Front 141

What are the virulence factors of C. difficile?

Back 141

- Flagellar proteins
- Surface layer proteins
- Surface exposed adhesion proteins

Front 142

When testing for C. difficile, what can you test for?

Back 142

NAAT (nucleic acid amplification test) only for Toxin B (only 2% of strains are toxin B negative)

Front 143

What are the characteristics of "hyper-virulent" strains of C. difficile?

Back 143

Large outbreaks during the last decade of BI/NAP1/027 strains:
- 16x more Toxin A
- 23x more Toxin B
- tcdC gene (toxin regulator gene) mutation may lead to increased toxin production(?)
- Increased fluoroquinolone resistance
- Mortality rates up to 6.9%

Front 144

What are the characteristics of Binary Toxin from C. difficile?

Back 144

- Found in BI/NAP1/027 strains (caused large outbreak in 2002)
- Unclear pathogenicity

Front 145

Which low risk populations are reporting more frequent reports of C. difficile? Possible source of infection?

Back 145

- Young
- Women in peri-partum
- No exposure to antibiotics

- Possible source: colonization and carriage reported in cows

Front 146

What are the typical symptoms of C. difficile infection?

Back 146

– Bloody watery diarrhea
– Fever
– Abdominal pain
– Leukocytosis
– Pseudomembranous colitis

Front 147

What are the severe / rarer symptoms of C. difficile infection?

Back 147

- Toxic megacolon
- Sepsis
- Colonic perforation
- Death

Front 148

What is this endoscopy indicative of?

Back 148

C. difficile (classic findings)

(these findings are not present in IBD patients with C. difficile)

Front 149

How do you prevent spread of C. difficile infection?

Back 149

• Wearing Gloves
• Hand hygiene/washing
• Alcohol based hand gels are in-effective against spore-forming organisms
• Isolation gowns
• Hand washing a must!
• Minimize exposure to antibiotics
• Environmental decontamination requires 10% sodium hypochlorite solutions

Front 150

Is there evidence for identifying or treating asymptomatic carriers of C. difficile?

Back 150

No

Front 151

What are the mainstay therapies for treating primary initial C. difficile infection?

Back 151

Vancomycin OR Metronidazole
- Similar efficacy in primary infection
- Few small differences
- Vancomycin may be more important for more severe infections

Front 152

What is the efficacy of Metronidazole for C. difficile infection?

Back 152

• Most cases treated successfully with metronidazole
• Doubling of C difficile associated disease between 1996-2003
• Diminished therapeutic response to metronidazole during this time
• Metronidazole less effective in severe infections

Front 153

What defines a severe disease state of C. difficile infection?

Back 153

Any one of the following:
- Age > 65 years
- Cr > 1.5x baseline
- WBC > 15K

Front 154

What complications can occur in severe C. difficile infection?

Back 154

- Hypotension / shock
- Ileus (obstruction in ileum)
- Megacolon (surgical emergency)

Front 155

What complication of C. difficile requires emergency surgery?

Back 155

Megacolon

Front 156

Patient with C. difficile has leukocytosis w/ WBC count of <15,000 cells/µL and a serum creatinine <1.5x premorbid level.

How is this classified and how should it be treated?

Back 156

Mild to moderate C. difficile
- Metronidazole 10-14 days

Front 157

Patient with C. difficile has leukocytosis w/ WBC count of >15,000 cells/µL or a serum creatinine >1.5x premorbid level.

How is this classified and how should it be treated?

Back 157

Severe C. difficile
- Vancomycin 10-14 days

Front 158

Patient with C. difficile has hypotension or shock, ileus, or megacolon.

How is this classified and how should it be treated?

Back 158

Severe and complicated C. difficile
- Vancomycin + Metronidazole (IV)
- If complete ileus, consider adding instillation of vancomycin
- If megacolon, emergency surgery

Front 159

How common is recurrence of C. difficile infection?

Back 159

10-35% of patients will experience recurrence of symptoms after initial infection

Front 160

What are the risk factors for C. difficile infection recurrence?

Back 160

– Continued Antibiotics
– Age & co-morbidities
– Antacid medication
– Immunosuppression?
– Immunodeficiency?

Front 161

How should you treat a patient with an uncomplicated recurrence of mild to moderate C. difficile?

Back 161

- Repeat initial therapy (Metronidazole)
- May consider switch to Vancomycin

Front 162

What is a "Vancomycin taper"? When is it utilized?

Back 162

Vancomycin PO 125mg:
- 4x/day for 10 days
- 2x/day for 7 days
- 1x/day for 7 days
- q48H for 7 days
- q72H for 14 days

(several variations, usually reserved for 3rd recurrence of C. difficile infection)

Front 163

What drug can you use after completing Vancomycin 125mg QID for 14 days for treating C. difficile infection that had treatment failure at least 4 times?

Back 163

Rifaximin for 2 weeks

Front 164

How effective is a Rifaximin chaser (2 weeks) after 14 day Vancomycin therapy?

Back 164

Resolution of symptoms in 87% (this is in patients who had treatment failure at least 4 times)

Front 165

What drug can be used to treat Cryptosporidiosis and Giardiasis, as well as being explored for C. difficile?

Back 165

Nitazoxanide

Front 166

What is Nitazoxanide used for? Mechanism?

Back 166

- Anti-parasitic used to treat cryptosporidiosis and giardiasis
- Also used for C. difficile (similar cure rate to Metronidazole)

- Interferes w/ e- transfer pathway needed for anaerobic metabolism

Front 167

What drug is an alternative to Vancomycin for C. difficile?

Back 167

Fidaxomicin

Front 168

What is the mechanism of Fidaxomicin? Uses?

Back 168

- Inhibits RNA polymerase (macrocyclic)
- Low serum concentration but high fecal concentration (stays in the GI tract where you want it)
- Effective on G+ aerobes and anaerobes (including C. difficile)
- Does not affect G- bacteria so it preserves GI flora

Front 169

How does Fidaxomycin compare to Vancomycin therapy for C. difficile?

Back 169

- Fidaxomycin had a lower recurrence rate
- However it is very expensive!! ($2800 for 10 day course)

Front 170

Are probiotics effective against C. difficile?

Back 170

Mixed results
- Some complications seen in immunocompromised and critically ill patients
- Fungemia from sacchromyces
- Endocarditis from lactobacillus and bifidobacteria
(Very rare complications)

Front 171

Which probiotic was studied in conjunction with Vancomycin and Metronidazole therapy? Efficacy vs placebo? Implications?

Back 171

Sacchromyces boulardii
- Lower failure rate compared to placebo for both initial infections and recurrent infections
* Patients experiencing at least 1 recurrent episode of C. difficile may benefit from S. boulardii

Front 172

What is a promising potential treatment for C. difficile that is still being studied?

Back 172

Fecal Transplant (symptoms improve in 73-100%, avg 83%)

Front 173

How does the humoral immune system respond to C. difficile? Evidence?

Back 173

Anti-toxin A and B antibody levels increase after resolved infection in most who avoid recurrence

Front 174

What is the benefit of having high IgA anti-toxin A (for C. difficile) as compared to low levels?

Back 174

High IgA anti-Toxin A 48x more protective against recurrence of C. difficile than low IgA anti-Toxin A titers

Front 175

How do asymptomatic carriers compare to patients with active C. difficile infection in terms of antibodies?

Back 175

Asymptomatic carriers have serum IgG anti-Toxin A that is 3x level in patients with infection

Front 176

How do the anti-toxin antibody levels compare in patients with prolonged C. difficile disease duration?

Back 176

The levels are notably longer in patients with prolonged infection

Front 177

What is the mechanism of IVIG for treating C. difficile? Utility?

Back 177

- Neutralization of Toxin A through IgG anti-Toxin A antibodies
- Data is not significant enough to indicate standard use

Front 178

Besides those listed already, what are some other potential therapies for C. difficile infection?

Back 178

• Monoclonal Antibodies (C. Diff toxin Ab, less recurrence)
• Teicoplanin (Europe only)
• Tigecycline IV (studied in severe disease only)
• Bacteriocin (bacterial peptides – experimental)

Front 179

78 y/o female with heart disease and emphysema was discharged from hospital 10 days ago after being treated for a community acquired pneumonia. She has developed bloody diarrhea with marked abdominal pain and is found to be C. diff positive. She is treated with Metronidizole, but on day 2 she become tachycardic, hypotensive and is moved to the ICU. She had a distended, tympanic and diffusely tender abdomen. An abdominal X ray shows a dilated colon. What is the next BEST treatment for this patient?

a) Add vancomycin
b) Add fidoximycin
c) Increase dose of metronidozole
d) Fecal transplant
e) Emergent colectomy

Back 179

Emergent colectomy - she already has megacolon, so she needs emergency surgery!

Front 180

What treatments should you consider for third and subsequent recurrences of C. difficile?

Back 180

- Vancomycin + S. boulardii
- Vancomycin + Rifaximin chaser
- Vancomycin + Rifampin
- Fecal transplantation
- Nitazoxamide
- IVIG

Front 181

What syndrome is associated with chronic and relapsing abdominal pain, bloating, and changes in bowel habits, including diarrhea and constipation?

Back 181

Irritable Bowel Syndrome (not a disease)

Front 182

What contributes to the pathogenesis of Irritable Bowel Syndrome?

Back 182

- Psychological stressors
- Diet
- Abnormal GI motility
- Visceral hypersensitivity

Front 183

When does Irritable Bowel Syndrome usually present? Who is more likely to have it?

Back 183

- 20-40 years of age
- Usually females
- 5-10% of people in developed countries
- Post-infection (continued GI symptoms following GI infection)

Front 184

What shows up on CBC, electrolytes, and LFTs for patients with Irritable Bowel Syndrome?

Back 184

All are normal

Front 185

What shows up on endoscopy and CT for patients with Irritable Bowel Syndrome?

Back 185

Normal stomach and intestines on both US and CT

Front 186

What are the Rome III criteria for Irritable Bowel Syndrome?

Back 186

Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months, associated with 2+ of the following:
1. Improves w/ defecation
2. Onset associated w/ a change in frequency of stool
3. Onset associated w/ a change in appearance or form of stool

Front 187

What is it called when there are outpouchings of the colonic mucosa and submucosa?

Back 187

Diverticular Disease (really pseudo-diverticular because not all 4 layers are involved)

Front 188

Structurally, what happens in Diverticular Disease?

Back 188

- Pseudo-diverticular out-pouching of colonic mucosa and submucosa
- Nerves and arterial vasa recta penetrate the inner circular muscle coat to create discontinuities in muscle wall

Front 189

Who is affected by Diverticular Disease?

Back 189

- Rare in persons < 30 yo
- Prevalence approaches 50% in Western adults > 60 yo

Front 190

When and where can Diverticular Disease develop?

Back 190

- Under conditions of elevated intraluminal pressure
- Most commonly in the sigmoid colon (but all areas of colon may be affected)
- May be exacerbated by diets low in fiber, which reduce stool bulk

Front 191

What can obstruction of the Diverticula in Diverticular Disease lead to?

Back 191

- Inflammatory changes, causing Diverticulitis →
- Perforation →
- Formation of pericolonic abscesses, development of sinus tracts, and occasionally, peritonitis

Front 192

What does this image show?

Back 192

Diverticular Disease

Front 193

What are the symptoms of Diverticular Disease?

Back 193

- Most asymptomatic
- 20% develop intermittent cramping, continuous lower abdominal discomfort, constipation and/or diarrhea

Front 194

What can possibly prevent Diverticular Disease?

Back 194

High-fiber diet

Front 195

How does Diverticular Disease resolve itself?

Back 195

- Often spontaneously
- After antibiotic treatment
- Few require surgical intervention

Front 196

Who is most commonly affected by Acute Appendicitis?

Back 196

- Most common in adolescents and young adults (but may occur at any age), lifetime risk is 7%
- Males more often than females

Front 197

What happens in 50-80% of cases of Acute Appendicitis?

Back 197

Overt luminal obstruction, usually a stone-like mass of stool or fecalith

Front 198

What triggers inflammatory responses in Acute Appendicitis?

Back 198

Ischemic injury and stasis of luminal contents, which favors bacterial proliferation

Front 199

What are the symptoms of Acute Appendicitis?

Back 199

- Early: periumbilical pain
- Later: moves to right lower quadrant
- Nausea, vomiting, low-grade fever, and mildly elevated WBC count
- McBurney's sign: deep tenderness noted at 2/3 distance from umbilicus to right anterior superior iliac spine

Front 200

What are the degrees of Ischemic Colitis?

Back 200

Mucosal infarction ⟷ Transmural infarction

Front 201

What causes mucosal infarction, resulting in ischemic colitis?

Back 201

Hypoperfusion, possibly from hypotension (eg, sepsis) or arterial spasm (eg, some medications)

Front 202

What causes transmural infarction, resulting in ischemic colitis?

Back 202

Arterial occlusion, possibly from acute arterial thrombosis or emoblis

Front 203

What part of the intestine is particularly susceptible to ischemia (ischemic colitis)?

Back 203

Intestinal segments at the end of their respective arterial supplies = "Watershed Zones"
- Splenic flexure
- Sigmoid colon and rectum

Front 204

What is the distribution of Ischemic Colitis? How is the mucosa affected?

Back 204

- Distribution is segmental and patchy
- Mucosa is hemorrhagic and often ulcerated

Front 205

What is the time course of Ischemic Colitis?

Back 205

- Self-limited
- Resolves when inciting event resolves (eg, hypotension is corrected)

Front 206

Who is affected by Ischemic Colitis?

Back 206

Tends to occur in older persons with co-existing cardiac or vascular disease

Front 207

What are the symptoms of Ischemic Colitis?

Back 207

Acute transmural infarction:
- Sudden, severe abdominal pain and tenderness
- Sometimes w/ nausea, vomiting, bloody diarrhea, or grossly melanotic stool

Front 208

A 13 year old otherwise healthy male reports to the ED with abdominal pain that started out near his umbilicus yesterday, but now it is in the right lower quadrant. He has a temperature of 101.5 and has a white blood cell count of 17.2. What is the the most likely diagnosis?

Back 208

Acute Appendicitis