Prunuske- C. Diff Case Study

Question 1

What is the prevalence of c. diff?

Answer 1

1. 500,000 Americans a year die from C. difficile infections (CDI)–many are acquired while in the hospital
2. C. diff- transmitted fecal-oral route and hospital workers and devices (fomite) may be intermediaries (nosocomial infection)
3. Acquired through the ingestion of endospores
4. Increase in incidence and severity possibly due to the emergence of more virulent strains like B1/NAP1/027, which produce more toxin as well as binary toxin

Question 2

What are the risk factors for CDI?

Answer 2

1. Carriers: 5-15% of adults, 84% of infants, and 57% of individuals in long term care facilities
2. Taking an antimicrobial or antineoplastic (anti-cancer drug–kill rapidly growing cells, bacteria fall into that category) in the last 2 months: disease has been reported following 1 dose of antibiotics. **Virtually every antibiotic is associated but broad spectrum are a particular concern.
3. Antibiotics diminish healthy bacteria allowing C. diff to multiply and begin producing toxins
4. Gastric acid suppression- proton pump inhibitor (Reduce stomach acid level, more likely to develop infections b/c acidic environment helps to sterilize what’s coming in)
5. Hospitalization (one of most common nosocomial infection)
6. Immunocompromised or elderly individuals

**Diminish healthy bacteria, which allows C. diff to multiply and become toxic

Question 3

Why do c. diff infections frequently reoccur?

Answer 3

1. Disruption of normal flora
2. Acquisition of c. Diff –>some people are just colonized but don’t become infected
3. Others get diarrhea
4. Some people resolve
5. Additional antibiotics make it worse

Question 4

What are the symptoms associated with C. Diff?

Answer 4

1. Mild disease: Present with fever, abdominal pain, watery diarrhea, and dehydration
2. Diarrhea is a key clinical feature- 3 or more loose stools for 1-2 days with no blood present, watery

Question 5

What is Pseudomembranous colitis?

Answer 5

1. Severe complications include perforation of colon, dehydration, death
2. Sepsis- inflammation leading to decrease in blood volume, interferes with organ function and can cause shock/death
3. Toxic megacolon becomes so swollen creating pressure on lungs making breathing difficult, colon relaxes, becomes so swollen makes breathing difficult

Question 6

What are differential diagnosis?

Answer 6

1. Diarrhea can be side effect from many antibiotics
2. Watery diarrhea is often caused by viruses (rotavirus, Norovirus) Bacteria (E. coli 157:H7, Vibrio cholerae, Campylobacter, Salmonella, Shigella, Yersinia, and Clostridium difficile)
   Protozoan (Giardia, Cryptosporidium, and Cyclospora)
3. Most of these infections are self-limiting and not life-threatening, but knowing cause is critical for choosing the correct antimicrobial

Question 7

What are the signs for a positive c. diff diagnosis?

Answer 7

1. Positive stool test for toxin (usually 3 samples)
2. Increased WBC>15,000 cells/mm3
3. Direct visualization by sigmoidoscopy of pseudomembranous colitis

Question 8

What is ELISA?

Answer 8

1. (enzyme-linked immunosorbent assay) to test for Toxin A and B, some strains are A-negative, B-positive
2. If target substance is present in immobilized sample then peroxidase enzyme
   generates purple color or can use fluorescence to detect toxin—only stable for 2hrs
3. ELISA has low sensitivity (60-80%) so recommending using nucleic acid amplification tests for toxin genes (NAA)–PCR primers specific to toxin used to amplify for toxin

**GDH is more sensitive but less specific, other organisms may give a positive result

Question 9

What are the components of pseudomembranous colitis?

Answer 9

Neutrophils, dead epithelial cells, and inflammatory debris

Question 10

What type of bacteria is c. diff?

Answer 10

Anaerobic, gram-positive rod, difficult to culture RECOGNIZE IMAGE

Question 11

What allows for the stability of c. diff (spore life cycle)?

Answer 11

1. Clostridium form endospores–allows for stability outside of the host in the soil.
2. Assymetrical cell division, forms sporangium, sporangium forms forespore, produces dense coat surrounding endospore. Creates free spore. Germination converts spore back to vegetative cell.
3. Produces more toxins than any other bacterial genius.

Question 12

What is the pathology of c. diff?

Answer 12

1. Normal microbiome suppresses C.diff growth
2. If microbiome is killed C. diff activated, toxins expressed
3. Both exotoxin A and exotoxin B bind receptors SPECIFICALLY in the colon walls and are glucosyltransferases that glucosylate RhoGTPase leading to the depolymerization of actin and death of enterocytes.
4. Toxin A (enterotoxin) activates the inflammatory cascade and disrupts the intercellular tight junctions causing fluid secretion, mucosal injury, edema, and inflammation.
5. Toxin B (cytotoxin) disrupts the cytoskeleton, leading to mucosal injury and activation of the inflammatory cascade.
6. Inflammation results in fever, watery diarrhea, increase in white blood cells

Question 13

How do you prevent the spread of c. diff?

Answer 13

1. Some of the EPA approved hospital disinfectants do not kill C. diff spores even though they said they did on the labels
2. Alcohol-based disinfectants are not effective against spore forming bacteria.

Question 14

What is decontamination?

Answer 14

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

Question 15

What is sterilization?

Answer 15

DESTROYS all living organisms, viruses, and endospores so they are no longer able to reproduce

Question 16

What is a disinfectant?

Answer 16

REDUCE organisms to a low enough level that disease is unlikely; INAMINATE objects since often too toxic to use on human tissues

Question 17

What is an antiseptic?

Answer 17

Microbicide safe to use on human tissue

Question 18

What is a sanitizer?

Answer 18

DECREASE number of microbes to a safe level but doesn’t eliminate

Question 19

What is an aseptic procedure?

Answer 19

Procedure performed under sterile conditions

Question 20

What factors effect sterilization?

Answer 20

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

Question 21

What is the decreasing order or resistance of micro-organisms to disinfection and sterilization?

Answer 21

Resistant
| Prions (Creutzfeldt-Jakob Disease)
| Bacterial spores (Bacillus atrophaeus, C. difficile)
| Coccidia (Cryptosporidium)
| Mycobacteria (M. tuberculosis, M. terrae)
| Nonlipid or small viruses (polio, coxsackie)
| Fungi (Aspergillus, Candida)
| Vegetative bacteria (S. aureus, P. aeruginosa)
↓ Lipid or medium-sized viruses (HIV, herpes, hepatitis B)
Susceptible

–enveloped viruses (hiv, herpes, hepatitis B) are easier to destroy, others are more likely to call GI effects b/c are less susceptible to being destroyed in your gut, harder to sterilize in external environment

Question 22

What chemicals can be used for sterilization?

Answer 22

1. Alcohol
2. Hydrogen peroxide
3. Chlorine
4. Iodophors
5. PHenolics
6. Glutaraldehyde

Question 23

What methods are there for sterilization?

Answer 23

1. Autoclave (no plastic)
2. Boiling-most pathogens, some spores
3. Pasteurization- vegetative bacteria, plastic equipment
4. Uv exposure
5. Ionizing radiation

Question 24

What is the best way to sterilize something that’s been in contact with c. diff?

Answer 24

Autoclave–saturated steam 121 degrees C

Question 25

What recommendations to help prevent c. diff outbreak in hospitals?

Answer 25

1. Track and report 2. Rapid identification and isolation: anyone admitted with diarrhea or antibiotic history is screened 3. Controls on antibiotics- limit those antibiotic use and track what prescriptions were being used by patients who contract C. diff 4. Strategies to minimize infections: wash hands and use gowns or gloves 5. Put individual in private room or in with another C. diff positive patient 6. Cleaning rooms with C. diff patients with dedicated or disposable toilet brush

Question 26

What meds should be used for treatment?

Answer 26

Mild- Metronidazole Severe- Vancomyacin (Give orally) Multiple recurrence- Fidaxomicin

Question 27

What other therapeutic treatments should be added to antibiotics?

Answer 27

1. Rehydration, stop offending antibiotics (20% of patients infection with resolve) 2. Don’t use antidiarrheal meds since they may slow down removal of bacteria and toxins prolonging infection 3. Don’t treat asymptomatic carriers 4. If perforations, surgery to remove colon and use of colonoscopy bag 5. Recurrence of symptoms is one of the challenges (5-47%) of cases (new antibiotic Fidaxomicin be better at preventing recurrence)

Question 28

When is fecal microbiota therapy used?

Answer 28

As a lost resort/to prevent relapse to restore colon with healthier microbiota