Clostridium difficile Lecture Sep 10

Question 1

What are the risk factors of CDI?

Answer 1

Recent antibiotic use (particularly with cephalosporins and clindamycin)

Exposure to the orgnism

Age

Immunocompromise

Residency in a hospital or long term health care facility

Recent GI surgery

Treatment with proton pump inhiitors

Question 2

What is the prevalence of CDI?

Answer 2

carriers: 5-10% of healthy adults; 84% of infants, 57% of long term care facility residents

500,00 Americans die annually from CDI

Question 3

WHy has there been an increase in severity?

Answer 3

Emergence of more virulent strains like B1/NAP1/027, which produces more tosin as well as binary toxin

Question 4

Who/what are the most common intermediaries of the disease?

Answer 4

Hospital workers and fomites (devices, toilets, etc) that are involved in the fecal-oral route of spore transmission

Question 5

What are the typical presentin symptoms of CDI?

WHat is the key clinical feature?

What will distinguish it from other bacteria that produce diarrhea?

Answer 5

PResent with fever abdominal pain, watery diarrhe, and dehydration

THe diarrhea is the key clinical feature

(3+ loose watery stools for 1-2 days)

Other bacteria will cause bloody diarrhea, whereas CDI is just watery

Question 6

What are some severe complications of CDI?

Answer 6

Perforation of the colon

Dehydration (severe)

Sepsis (inflammation leading to decrease in blood volume)

Toxic megacolon–colon becomes so swollen that it creates pressure on the lungs making breathing difficult

Question 7

What would be in the differential?

Answer 7

1. DIarrhea as a side effect of ABx
2. viruses like rotavirus and norovirus
3. Other bacteria such as vibrio cholerae, campylobacter, salmonella, shigella, yersinia,
4. Protozoa infection with giardia, cryptosporidium, and cyclospora
5. none-infectious diseases resulting in diarrhea, like crohn’s, IBD, etc

Question 8

What tests are used to diagnose CDI?

Answer 8

Increased WBC suggest infection

You can do positive stool test for toxins

Direct visualization by sigmoidoscopy of pseudomembranous colitis

To test for toxin:

1. use an ELISA (but toxin is only stable for 2 hours).
2. Use NAAT to do PCR for toxins
3. do CCNA to check for toxins

OTher tests:

Use GDH as a screening tool (more sensitive, but less specific)

Question 9

WHat does CDI look like on a gram stain?

Answer 9

Gram positive rods–single. Anaerobic.

Question 10

WHy is clostridium so hard to destroy in the environment?

Answer 10

It can form endospores, allowing for stability outside of the host.

Question 11

Describe the process of sporulation.

Answer 11

THe vegetative cell realized conditions are no longer ideal

1. THe chromosome is duplicated and separated
2. the cell is septated into sporingium and forespore
3. The sporangium englufs the forespore
4. Sporgnium being to synthesize spore layers around the forespore
5. Cortex and outer layers are deposited
6. Mature endospor is released from the sporangium.
7. When favorable conditions are reached, the spore germinates and releases a vegetative bacteria.

Question 12

What bacterial genus produces toxins more than any other?

Answer 12

Clostridium

(but not all are toxigenic)

Question 13

How does C diff cause pathology?

Answer 13

Produces toxins: all produce B and some protude A as well.

BOth exotoxin A and B bind receptors in the colon walls and are glycosyltransferases that glucosylate RhoGTPase leading to the depolymerization of actin and death of enterocytes

Toxin A (enterotoxin) activates the inflammatory cascae and disrupts the intercellular tight junctions causing fluid secretion, mucosal injury, edema, and inflammation

Toxin B (cytotoxin) disrupts the cytoskeleton, leading to mucosal injury and activation of the inflammatory cascade.

Inflamation results in fever, watery diarrhea, and increased WBC

Question 14

What are some of the virulence factors of C diff?

Answer 14

Exotoxins A and B

Polysaccharide capsule to block phagocytosis

Flagella for motility

Question 15

Will alcohol-based disinfectant be effective against spore-forming bacteria?

Answer 15

No

Question 16

What is decontamination?

What is sterilization?

What is disinfectant?

What is antiseptic?

What is sanitizer?

What is aseptic?

Answer 16

Decontamination- occurs prior to sterilization doesn’t remove microbes but removes chemicals, radioactivity to make safe to handle

Sterilization- destroys all living organisms, viruses, and endospores so they are no longer able to reproduce

Disinfectant- reduce organisms to a low enough level that disease is unlikely; inanimate objects since often too toxic to use on human tissues

Antiseptic- microbicide safe to use on human tissue

Sanitizer- decrease number of microbes to a safe level but doesn’t eliminate

Aseptic- procedure performed under sterile conditions

Question 17

What are 6 factors that effect sterilization?

Answer 17

1. Concentration of microbe or chemical
2. Time over which the agent is applied
3. Temperature (higher temp, less time)
4. Type of orgnism
5. Material bearing the organism (dirt)
6. May affect normal flora

Question 18

Why might abscence of growth not prove sterility?

Answer 18

THe culture may not be at the right temp, pH, O2 level, or nutrients.

It may need more time as well.

Question 19

Rank the following from most resistant to most susceptible to disinfection and sterilization:

Fungi

Mycobacteria

COccidia

Prions

Bacterial SPores

Nonlipid or small viruses

Vegetative Baceria

Lipid or medium sized viruses

Answer 19

Resistant:

Prions

Bacterial spores

Coccidia

Mycobacteria

Nonlipid viruses

Fungi

Vegetative bacteria

Lipid or medium sized viruses

Suseptible

Question 20

What is the method of choice for sterilization in C diff.

WHat are some other options?

Answer 20

Autoclaving (steam at 121 degreed C) is the only thing that will actually sterilize

FOr plastic equipment though, you can use chlorine bleach (this will disinfect), radiation, or UV

Pasteurization would only kill vegetative bacteria, not spores

Question 21

What are six recommendations to help prevent C diff infection in hospitals?

Answer 21

1. track and report cases
2. rapid identification and isolation (anyone admitted with diarrhea or antibiotic history is screened)
3. Controls on antibitics–limit those antibiotic use and track what prescriptions were being used by patients who contract C diff
4. Strategies to minimise infections: hand washing, PPE
5. Put those infected in private rooms or in with another C diff positive patient
6. Cleaning rooms with C. diff patients wiht dedicated or disposable toilet brush

Question 22

What is the treatment of choice in mild cases? What’s the mechanism of action?

What is the treatment of choice in severe cases/recurrent cases? WHat’s the mechanism of action?

What is the third drug available?

Answer 22

Metornidaxole is the first choice, and it works by causing DNA damage thorugh an increase in ROS.

Vancomycin is the antibiotic for severe cases, and it works by blocking cell wall synthesis.

The third drug is Fidaxomicin

Question 23

What are some other treatment steps besides drugs?

Answer 23

1. Stop the offending antibiotic (resolves 20% of cases)
2. Rehydrate
3. Surgery for perforations
4. Fecal transplant for recurrences

Question 24

What are treatments you shouldn’t order?

Answer 24

Don’t treat someone who’s just a carrier.

Don’t treat with antidiarrheal meds.