Clostridium difficile Flashcards
What is the characteristics of C diff?
- anaerobic, grame positive, spore forming, exotoxin producing bacilli
- colonizes 3% of adults, 20-50% of hospitalized patients (fecal-oral transmission)
- C. difficile enterotoxin A and cytotoxin B causes inflammation, fluid secretion (diarrhea), neutrophilic colitis, mucosal injury
As long as we have _______, the c difficile is stable and steady and kept under check
normal flora
What part of the C difficile is toxic to the colon?
- the c diff toxin
Why are most C diff infections recurrent?
- most of these infections are recurrent because there is something in the bug spores that go dormant and stay in the intestine
What is the NAP1 strain of bacteria?
- extremely virulent strain of c diff - hyper producing toxin C. perfringens type toxin (patients are needing to undergo removal or a part of their intestine)
Selecting out the NAP1 stain is associated with ____ use
quinolone (clinda)
What is associated with NAP1 strain of bacteria?
- higher rates of treatment failure
- recurrent 2x
- complications 2x
- and attributable mortality compared with non-NAP1
What are the risk factors associated with C. diff?
- antimicrobial therapy that disrupts the normal colonic flora, typically presents within 4-9 days (to 8 weeks)
- hospitalization over 72 hours
- female and advanced age over 65 years
- multiple co-morbidities, severe underlying disease, immunocompromised
- gastric acid suppression (antacids), enteral feeding, GI surgery, inflammatory, bowel ds, immunocompromised
What is the antibiotic that puts patients at the highest risk of C diff?
- clindamycin
What are other high risk medications for C diff?
- fluoroquinolones
- cephalosporins
- penicillins
What are the clinical signs of infections and complications of CDI?
- watery diarrhea with over 3 unformed stools in 24 hours
- nausea, vomiting, abdominal pain, high fever, significant leukocytosis (high WBC >10,000)
What are the complications of C. diff?
- septic shock, pseudomonas or fulminant colitis, ileus, toxic megacolon, perforation
(intestine is so inflamed or ulcerated- layers of the gut starts to be separated- need surgery here because the gut is not going to recover)
How is CDI diagnosed?
- symptoms with diarrhea and positive C. difficile toxin in stool
- culture and molecular typing during outbreaks
How many days would it take for antibiotics to alter the normal flora of the gut?
- 4-5 days of antibiotic use
When are probiotics most useful in patients?
- they are the most beneficial when you target the probiotics on people that are on the highest risk of c diff (elderly, IBD, many comorbidities)
List the important strategies for preventing CDI?
Infection control
- environmental cleaning and disinfecting
- healthcare worker hygiene, hand washing (alcohol based sanitizers not effective against spores)
- contact barrier precautions
Antimicrobial stewardship
What is procedure for patients with confirmed cases of CDI?
- single rooms for those with known CDI
What is the general approach to treating CDI. How does treatment change for severe infection?
- discontinue offending antimicrobial and replace with lower risk agent if warranted
- initiate supportive measures for hydration and electrolyte balance
- initiate antimicrobial therapy for c. difficile infections
- avoid anti-motility agents
- implement infection control measures
- surgery for severe, complicated disease
Is there any benefit in reducing the dose of the antibiotics to prevent C diff?
- NO
- it will still have the same risk of C diff no matter the dose
- the best that you could do is to pick out an antibiotic that is of a lower risk of causing C diff (tetracyclines, aminoglycosides)
What are the 2 drugs that have C diff coverage?
metronidazole and vancomycin are the 2 drugs that have c diff coverage
How long of a treatment of metronidazole is needed for C diff infections?
10-14 days, and for 7 days beyond the discontinuation of the offending agent or other therapy
What antibiotic is preferred to treat C diff and why?
- metronidazole
- lower risk of collateral resistance and cost response
- should see a clinical important within 2 days and diarrhea resolution within 5-7 days
What are the signs of treatment failure associated with metronidazole?
- fever over 3 days, GI symptoms over 5 days or worsening or deteriorating clinical status during therapy
- 5-20% recurrence rate
What are the adverse effects associated with metronidazole?
- GI, metallic taste, disulfiram reaction, CNS, peripheral neuropathy or neurotoxicity
Why do metronidazole and vancomycin work to treat C diff bacteria?
- they target the intestine
- they have a chance of selecting out the enterococcus in the intestine
What is the real concern about C diff? Is the enterococcus very virulent?
- enterococcus is not very virulent
- not a bug that really causes bad disease, this bacteria affects the immunocompromised however
- if we got vance resistance (which can be in c diff) in staph aureus then that would be a catastrophe (would be a real concern because the enterococcus and the staph aureus are both gram positive and share ribosomes and information)
What is the theory for why there is treatment failure in metronidazole?
- failure with metronidazole is due to insufficient concentrations in the colon
- when metronidazole hits the small intestine and the stomach- the drug is absorbed in the stomach so in some cases not a lot goes down to the colon (will cause failure of metro)
Vancomycin is preferred in what cases?
- pregnancy and lactation
- metro intolerance or failure
- severe infection
Is vancomycin absorbed in the body?
- no- vancomycin is not absorbed
- it is not used at all in any systemic infection because it does not leave the gut (for a c. diff infection this is a good thing)
- this is the ONLY thing that you would use an oral vancomycin for
If the person was totally NPO, what drug would be the best to give then via IV?
- we would want to give the person IV metronidazole
- if we gave IV vance then it would not be in the gut at all and would not be effective to us at all
What is the adverse effect profile of vancomycin vs metronidazole?
- there are fewer adverse effects of vance compared to metronidazole
What are the risk factors for a severe C diff infection?
- advanced age
- debilitated
- inflammatory bowel disease
- immunocompromised
For mild to moderate disease, you always use ____
metronidazole
For severe disease, you always use ______
vancomycin
What do you use in the case of a very severe infection?
- vancomycin as a retention enema, as well as metronidazole IV
What constitutes a very severe infection?
- if a persons WBC count is under 2000 they are septic and have a very severe infection
What is the definition of a recurrent CDI infection?
symptoms of positive C diff toxin within 8 weeks of initial episode
- first recurrence in 20-25% with multiple recurrences in 65% thereafter
What is a recurrent CDI caused by?
- related to persistent spores and/or low antitoxin antibodies, not antimicrobial resistance
If a person has recurrent CDI infections, what should they consider using?
probiotics
What is the treatment plan for the FIRST recurrence of C diff in a patient?
- repeat initial therapy if consistent with severity, response rate 50%
What is the treatment plan for multiple recurrences
- Vancomycin pulsing or tapering recommended in guidelines despite weak evidence
What is fidaxomicin?
- macrocyclic bactericidal antimicrobial with poor po absorption
- non inferior compared to Vancomycin for initial episodes, but lower recurrence rate 15-20% versus
- limited data for treating recurrent CDI
When are fecal microbiota transplants used?
- they are used as an adjuvant to antimicrobial therapy
- collected from a healthy donor and delivered via nasogastric, nasojejunal, gastrostomy tube, colonoscopy or enema
What is the purpose of a fecal microbiota transplant?
- alters and increases the diversity of the gut microbiota
