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Clostridium difficile- a brief review for clinicians

Clostridium difficile


Clostridium difficile is a bacterium that is the most common cause of hospital acquired diarrhea.
Diarrhea due to Clostridium difficile can cause significant morbidity and sometimes mortality in the hospitalized patient. Diarrhea from this often adds to unnecessary additional hospitalization days and treatments.
The diarrhea can be refractory to treatment and can be the cause of recurrent diarrhea.
The occurrence of hospital acquired Clostridium difficile associated diarrhea (CDAD) is used as a marker of healthcare quality and factors into a hospitals overall scorecard. This will be a point in the future hospitals value based purchasing.

The following recommendations are extracts from Clinical practice guidelines for Clostridium difficle infection in Adults[1]


Clostridium difficile (CD) is an anaerobic spore forming organism that is the commonest cause of hospital acquired diarrhea.
Clostrdium difficile with spores

CD produces toxins (A & B) that can bind to colonic endothelium and result in excess secretion of fluid leading to diarrhea. Some colonic wall inflammation can be produced that in severe cases results in severe enterocolitis. This is a significant cause of nosocomial morbidity and mortality.


Clostridium difficile infection (CDI)

Presence of diarrhea with either toxin positive stool or pseudomembranes identified on endoscopy.


Diarrhea is further defined as three or more unformed stools in a 24 hour period.

Transmission- current understanding

Clostridium difficile is a transmittable nosocomial pathogen[2]. Time between exposure and onset of symptoms can be as short as three days.

Most patients are CD negative on admission. Up to 30% of patients are CD positive but symptoms negative on discharge. It is believed therefore that acquisition can frequently occur in house. A subset of patients will go on the develop symptoms. [2]

It is therefore believed that transmission of spores from patient to patient occurs through asymptomatic transient healthcare provider hand contamination.[2] Attention to hand washing will break this potential transmission.

Newly colonized patients who are now subjected to alterations in the colonic bowel flora by antibiotics, proton pump inhibitors or colonic enemas will have their bowel flora changed in favor of the CD and will often go on the develop symptomatic CDAD.

Risk factors for disease

  1. Age: greater than 64 [3]
  2. Antibiotics: all antibiotics even single doses have been associated with CDI
  3. PPI: reduction in gastric acid does increase the risk of spores reaching the colon[4]
  4. Gastointestinal surgery [5]
  5. Feeding tubes [6]


  • Done only on unformed stools
  • Testing of stool from asymptomatic patients is not useful and should not be done as a test for cure
  • Repeat testing during the same episode should not be done
  • Tests
    • Toxin assay: fast turn around but not very sensitive
    • PCR assay: fast turn around and very sensitive, does not differentiate between active infectiona and colonization- more recent availability


  1. Stop offending agents
    1. Minimizing the duration of antibiotic therapy and the spectrum of activity can reduce the duration of illness.
  2. Start empiric treatment if symptoms severe enough
    1. Metronidazole: Still first line therapy, inexpensive but can cause neuropathy with prolonged use.
    2. Oral vancomycin: If no significant improvment in 48 hours should switch to oral vancomycin 125mf four times per day. No added benefit from higher doses.
      1. Capsule: Typically dispensed by retail pharmacies if the liquid is not specifically requested and is very expensive. About $80 per day.
      2. Li quid Vancomycin: compounded by a pharmacist from a bag of IV Vancomycin is much more affordable. Aprox $30 for a month but not all pharmacies with dispense it.
    3. Fidoxamicin: Recently introduced. Currently not a first line agent. Expensive.
  3. Avoid antimotility agents like lomotil
  4. Colectomy for severe cases

Role of probiotics

  • Method of action?: Unclear how use of yeast re-establishes displaced colonic flora
  • Formulations: unstandardized
  • Data to support use?
  • Adverse effects: Risk of fungemia
  • Not recommended for primary prevention

Role of Questran

  • Mechanism of action: By binding to toxin it is believed to reduce exposure to the colonic mucosa. It can also absorb vancomycin in the bowel lumen. Not clear that it reduces duration of illness.
  • Patient tolerability

Infection control

Recomendations for active cases

  1. Gown and glove
  2. Wash hands with soap and water after caring for patients with CDAD. [7]
  3. Terminal cleaning with bleach containing cleaning agents with sufficient dwell time to disinfect surfaces.
  4. Use single use medical devices when possible.
  5. Food service handling: Do not enter room. Food try taken into room by floor staff. Used trays are moved to dirty utility room.


  1. Handwashing between all patients [7]
  2. Judicious use of PPI [4]
  3. Antibiotic stewardship
    1. Appropriate choice of drug: restricting use of cephalosporins (except for surgical prophylaxis) and clindamycin can reduce the risk for CDI
    2. Optimal duration: minimize the duration of antibiotic therapy can reduce the risk for CDI
  4. Standardize environmental cleaning
  5. Routine environmental and personnel screening for clostridium difficile is not recommended

When to retest a patient

The short answer is probably never to retest. If the patient is clinically better then there is no indication to retest. Most patients will remain PCR or toxin positive for weeks after clinical improvement is seen.
Asymtomatic colonized patients appear to be at lower risk of development of CDI than higher. [2]


When to discontinue contact precautions?

  • After diarrhea has resolved
  • Patient is continent of stool
  • Patient is able to take a shower

Thereby reducing the environmental contamination

What about relapsers?

  • Tapering dose of vancomycin over weeks
  • Pulse: Once week on and then a few days off. Restart when symptoms recur. The logic is that vancomycin acts on vegetative forms of CD and that giving a holiday from vancomycin will allow some spores to germinate. It is hoped that the spore reservoir is eventually exhausted.
  • Fecal transplant: Historically shown in case reports to be successful but has serious obvious limitations to widespread use due to the concern for transmission of other pathogens.

What about chronic positives without symptoms?

  • No treatment recommended
  • They do not appear to go on and have symptomatic disease

Summary of Recomendations

  • Healthcare workers and visitors must use gloves and gowns on entry to a room of a patient with CDAD
  • Physicians should be made aware of the current situation to increase their “buy-in” to the process
  • Visitors and healthcare workers must use soap and water after caring for patients with CDAD
  • Contact precautions will be maintained for the duration of diarrhea
  • Routine screening or treatment of asymptomatic patients is NOT recommended
  • Environmental testing is NOT recommended
  • Healthcare worker colonization is low, therefore screening is not recommended [8]
  • Environmental cleaning with chlorine based product is recommended. Current practices should be reviewed.
  • There is limited data to support the use of probiotics for treatment or prevention
  • Avoid anti peristaltic agents
  • Discontinuation of antimicrobial use as soon as possible is recommended
  • Efforts to identify common personnel (to find the culprit) between cases is not recommended. It is unlikely that this is a single person but rather a cultural issue. We are all to blame.
  • Continued surveillance for new cases

PPIs increase the risk for clostridium difficile says FDA

Last month the Food and Drug administration (FDA) formally put out an alert linking the risk of proton pump inhibitors (PPI) to clostridium difficile  associated diarrhea. Though this has been known for some time it was only now that the concerns have been raised to the level of a safety alert.

The PPIs are often viewed as a safe class of drug and are often started for valid reasons but not stopped even after the original indication is gone. As the incidence of recurrent and refractory clostridium difficile  becomes an every growing problem especially in the elderly who are often on PPIs it is becoming necessary to evaluate the risks and benefits of continuing PPIs long term.

 Bottom line: Stop PPIs if there is not longer a clear reason to be taking them.


Safety Alerts for Human Medical Products > Proton Pump Inhibitors (PPIs) – Drug Safety Communication: Clostridium Difficile-Associated Diarrhea (CDAD) Can be Associated With Stomach Acid Drugs.

IDSA and SHEA have new guidelines on clostridium difficile

Clostridium difficile has gone from being just a nuisance or an everyday major problem today. Research has been ongoing to look for better treatment plans and strategies for dealing with relapses. The Infectious Disease Society of America (IDSA) and The Society for for Healthcare Epidemiology of America (SHEA) have released updated guidelines in the May 2010 issue of Infection Control and Hospital Epidemiology.

The guidelines are helpful in reviewing the current state of the art with regards to treating this problem. With the number of remedies and regimens it is important to decide what works and what does not have the science to back it up.
A few points to emphasize from this document that are relevant for day to day practice.

1. Stools should not be checked in asymptomatic patients: This sounds simple enough but unfortunately I get a call almost every week from the lab asking what they should do with a solid stool specimen sent to them for clostridium difficile assay. Stools will remain toxin positive and PCR positive in patients successfully treated for months. There is no value in retesting stools.

2. Repeat testing of stool for toxin during the same episode of diarrhea should not be done.

3. Gloves AND gowns are recommended for all healthcare workers and visitors. There is good evidence that this does reduce nosocomial transmission. This has remained standard practice but unfortunately is often the least adhered to.

4. Private rooms are preferred but if private rooms are not available, cohorting is acceptable with a dedicated commode for each patient.

5. Chlorine containing cleaning agents should be used to reduce spore transmission, there was no recommendations with regards to changing curtains etc.

6. Environmental culture for clostridium difficile is not recommended.

7. Probiotics: Primary use of probiotics to prevent clostridium difficile is not recommended. There are no trials that support the theory that it will prevent clostridium difficile.

8. Metronidazole still remains the first line of therapy it is also recommended for relapse. But should not be used for long term therapy due to risk of neurotoxicity.

9. Treatment of greater than two recurrences can be done with vancomycin with either tapering or pulse treatment. Jury still appears to be out with clear guidelines on what should be done with frequent relapsers.

10. Though is is still very frequently used there is no evidence that use of rifampin or cholestyramine reduces the risk of future recurrence. In fact cholestyramine may delay recovery as it bind to the antibiotics in addition to the toxin.

11. Some practitioners use rifaxamin for the treatment of clostridium difficile with PO vancomycin. The only study on this was small study of 8 patients, where rifaxamin was used immediately after finishing the course of vancomycin it reduced the number of future relapses in 7 of the patients. A very small study and difficult to base widespread use of the agent based on this alone.

12. There is no compelling evidence that use of probiotics are useful in prevention or treatment of clostridium difficile. These agents are widely used with the general feeling that it “cannot hurt”. I am not sure that there is any evidence of this either. In fact there are cases of fungemia due to this.

There is ongoing study in the area of use of immunoglobulin for the prevention and treatment of refractory clostridium difficile. Widespread use cannot still be advocated.

Clostridium difficile remains an important disease and there remains a need for better understanding of the treatment especially in those with frequent relapses and refractory disease.