L7- GI Infections II (C. diff.)

Question 1

(1) is the main causal agent of Intra-abdominal abscesses. It has (2) microbal features. (1) is also associated with (3) infections and in the GIT is usually secondary to (4) infections.

Answer 1

1- Bacteroides fragilis
2- Gram(-), anaerobic, non-spore forming rod (GNAR), apart of normal colon flora
3- (opportunistic infections) GYN abscesses, skin/soft-tissue infections, bacteremia (1/2 of cases caused by GNAR)
4- E. coli (takes up oxygen => anaerobic environment)

Question 2

Intra-abdominal Abscess:

• one of the following three events, (1), allows for dissemination of (2)
• (2) will then (3) to its site and the presence of (4) induces abscess formation
• (5) feature allows for intrinsic antibiotic resistance
• it is importantly noted (6) is not a factor

Answer 2

1- trauma, intestinal cancer, surgery
2- Bacteroides fragilis
3- fimbriae --> adhesion
4- polysaccharide capsule
5- β-lactamases
6- LPS (no pyrogenic activity)

Question 3

Antibiotic-associated colitis refers to (1) infection mainly, with (2) microbial features. It is a major (3) pathogen in terms of spread / distribution. It can come in (4) forms

Answer 3

1- Clostridium difficile
2- Gram(+) bacillus, anaerobic, endospore-former
3- nosocomial
4- Toxigenic A/B strains (+ hypervirulent epidemic strain)

Question 4

C. diff. is found in (1) in environment and is spread via (2). Colonization may lead to (3).

Answer 4

1- (widespread) soil, food, water
2- Health Care Worker hands, environment
3- C. diff. infection or associated disease, or asymptomatic

Question 5

after use of antibiotic it takes (1) amount of time to replace normal microbiota

post-antibiotic use, C. diff. infections are common, as (2) are more available in the GIT, allowing for (3)

Answer 5

1- 4wks - 6mos

2- bile acids
3- conversion of C. diff. spores –> germination / infection

Question 6

list the range of clinical features of C. diff. infections

Answer 6

Mild- self-limiting diarrhea
Moderate- pseudomembrane colitis (PMC)
Severe- toxic megacolon

Generally: 3 loose/watery stools per day, anorexia, nausea, leukocytosis (neutrophilia)

Question 7

describe the risk factors for C. diff. infections

Answer 7

1) antibiotic use: risk in with duration and number of antibiotics

2) antibiotic type:
- clindamycin - high
- penicillins - medium
- aminoglycosides - low

3) age, >65y/o
4) hospitilization (prior hosp. or lengthy hosp.)

Question 8

describe the basic C. difficile pathogenesis

Answer 8

1) spore ingestion
2) spore germination
3) attachment
4) toxin production
5) actin depolymerization / cell death
6) inflammatory cascade

Question 9

C. difficile:

• (1) toxins
• (2) disrupts actin cytoskeleton
• (3) other virulence factors (hint- 3)

Answer 9

1- toxin clostridium difficile: TcdA, TcdB

2- glycosylate guanosine triphosphase

3- flagella, adhesins, surface proteins/polysaccharides

Question 10

describe the structure of C. difficile toxins

Answer 10

(TcdA, TcdB)
A- biological activity: transfers glucose to inactivate GTPase involved in cytoskeleton regulation => cytoskeleton breakdown and cell death

B- binding
C- cutting (cleavage of toxin)
D- delivery (endocytosis, translocation)

Question 11

describe C. difficile diagnosis (include what is NOT used)

Answer 11

i) clinical Sxs

ii) Dx testing:
- NAAT 1-3 hrs (high sensitivity / specificity), doesn’t identify active toxin production
- EIA for GDH Ag (glutamate dehydrogenase)
- EIA for toxins A/B

NOT used:

• culture
• cell culture cytotoxicity

Question 12

list the top 5 causal agents of food-borne GIT infections

Answer 12

1) norovirus, 48%

Bacteria, 46%

2) salmonella
3) clostridium perfringens
4) campylobacter
5) S. aureus

Question 13

compare acute, persistent, chronic diarrhea

Answer 13

*Acute- <2 wks (most common)

Persistent- 2-4 wks

Chronic- >4wks

Question 14

most causes of chronic diarrhea are….

Answer 14

• drugs
• non-infectious causes
• *parasites

Question 15

Acute diarrhea:
(1) type: feces description, site affected, definition, associated Sxs, causal agents

(2) type: feces description, site affected, definition, causal agents

Answer 15

Non-inflammatory:

• watery, non-bloody diarrhea
• SI
• mucosal hypersecretion / dec absorption w/o mucosal destruction
• abrupt onset + fever; systemic Sxs usually absent
• viruses, non-invasive bacteria

Inflammatory:

• bloody, pussy diarrhea
• colon
• mucosal invasion w/ inflammation
• invasive bacteria, toxin-producing bacteria

Question 16

what are the 3 things to note when taking history for an acute diarrhea and suspecting an infectious cause

Answer 16

(each will have specific micro-organism associations)

• Foods (and how they’re prepared)
• Exposures (swimming, hospital, pets, etc)
• Demographic groups

Question 17

List common causal agents for diarrhea based on incubation period:

• (1) very short, minutes to hrs
• (2) 24hrs - 7 days
• (3) >7 days to wks/mos

Answer 17

1- B. cereus, S. aureus, marine toxins, fungal toxins

2- many, many, many

3- parasites, liver infections (HepA), listeriosis (L. monocytogenes)

Question 18

what is the key initial treatment in all severe diarrheas

Answer 18

treat dehydration then look for underlying infections:

• ORT (oral rehydration therapy)
• IV rehydration

Question 19

list the signs and symptoms that encourage additional testing for infectious diarrhea

Note-most are self-limiting and diagnosed clinically

Answer 19

• severe dehydration / illness
• severe abdominal cramping / tenderness
• persistent fever
• bloody / mucoid stool = inflammatory diarrhea
• signs of sepsis
• immunocompromised Pts
• suspected nosocomial infection / outbreak
• older Pts with comorbidities

Question 20

list the many classic stool investigations

Answer 20

1) stool lactoferrin WBS (indicates inflammatory diarrhea)
2) stool RBCs (indirect)
3) ova / parasites / Giardia Ag if: diarrhea >7days, AIDS / MSM, community waterborne outbreak, bloody diarrhea w/o fecal leukocytes
4) culture (E. coli, salmonella, shigella, campylobacter)
5) culture independent tests: PCR
6) C. difficile toxin (if on or previously on antibiotic Tx)

Question 21

describe general use of antibiotics in diarrhea diseases

Answer 21

NOT in adults with non-severe, non-bloody diarrhea

YES in:
-febrile w/ signs of invasive disease
-persistent infection >7days
-severe Sxs (>8 stools/day)
(-hospitalization may be required)