Clostridium difficile Lecture Sep 10 Flashcards
What are the risk factors of CDI?
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
What is the prevalence of CDI?
carriers: 5-10% of healthy adults; 84% of infants, 57% of long term care facility residents
500,00 Americans die annually from CDI
WHy has there been an increase in severity?
Emergence of more virulent strains like B1/NAP1/027, which produces more tosin as well as binary toxin
Who/what are the most common intermediaries of the disease?
Hospital workers and fomites (devices, toilets, etc) that are involved in the fecal-oral route of spore transmission
What are the typical presentin symptoms of CDI?
WHat is the key clinical feature?
What will distinguish it from other bacteria that produce diarrhea?
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
What are some severe complications of CDI?
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
What would be in the differential?
- DIarrhea as a side effect of ABx
- viruses like rotavirus and norovirus
- Other bacteria such as vibrio cholerae, campylobacter, salmonella, shigella, yersinia,
- Protozoa infection with giardia, cryptosporidium, and cyclospora
- none-infectious diseases resulting in diarrhea, like crohn’s, IBD, etc
What tests are used to diagnose CDI?
Increased WBC suggest infection
You can do positive stool test for toxins
Direct visualization by sigmoidoscopy of pseudomembranous colitis
To test for toxin:
- use an ELISA (but toxin is only stable for 2 hours).
- Use NAAT to do PCR for toxins
- do CCNA to check for toxins
OTher tests:
Use GDH as a screening tool (more sensitive, but less specific)
WHat does CDI look like on a gram stain?
Gram positive rods–single. Anaerobic.
WHy is clostridium so hard to destroy in the environment?
It can form endospores, allowing for stability outside of the host.
Describe the process of sporulation.
THe vegetative cell realized conditions are no longer ideal
- THe chromosome is duplicated and separated
- the cell is septated into sporingium and forespore
- The sporangium englufs the forespore
- Sporgnium being to synthesize spore layers around the forespore
- Cortex and outer layers are deposited
- Mature endospor is released from the sporangium.
- When favorable conditions are reached, the spore germinates and releases a vegetative bacteria.
What bacterial genus produces toxins more than any other?
Clostridium
(but not all are toxigenic)
How does C diff cause pathology?
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
What are some of the virulence factors of C diff?
Exotoxins A and B
Polysaccharide capsule to block phagocytosis
Flagella for motility
Will alcohol-based disinfectant be effective against spore-forming bacteria?
No
What is decontamination?
What is sterilization?
What is disinfectant?
What is antiseptic?
What is sanitizer?
What is aseptic?
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
What are 6 factors that effect sterilization?
- Concentration of microbe or chemical
- Time over which the agent is applied
- Temperature (higher temp, less time)
- Type of orgnism
- Material bearing the organism (dirt)
- May affect normal flora
Why might abscence of growth not prove sterility?
THe culture may not be at the right temp, pH, O2 level, or nutrients.
It may need more time as well.
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
Resistant:
Prions
Bacterial spores
Coccidia
Mycobacteria
Nonlipid viruses
Fungi
Vegetative bacteria
Lipid or medium sized viruses
Suseptible
What is the method of choice for sterilization in C diff.
WHat are some other options?
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
What are six recommendations to help prevent C diff infection in hospitals?
- track and report cases
- rapid identification and isolation (anyone admitted with diarrhea or antibiotic history is screened)
- Controls on antibitics–limit those antibiotic use and track what prescriptions were being used by patients who contract C diff
- Strategies to minimise infections: hand washing, PPE
- Put those infected in private rooms or in with another C diff positive patient
- Cleaning rooms with C. diff patients wiht dedicated or disposable toilet brush
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?
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
What are some other treatment steps besides drugs?
- Stop the offending antibiotic (resolves 20% of cases)
- Rehydrate
- Surgery for perforations
- Fecal transplant for recurrences
What are treatments you shouldn’t order?
Don’t treat someone who’s just a carrier.
Don’t treat with antidiarrheal meds.
