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Clostridium Difficile. Stratification and Treatment Patient Case Robert Thompson PharmD Candidate Intermountain Medical Center August 9, 2013 . Learning objectives. Describe the roll of good intestinal flora Identify the epidemiology and pathophysiology of Clostridium difficile

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clostridium difficile

Clostridium Difficile

Stratification and Treatment

Patient Case

Robert Thompson PharmD Candidate

Intermountain Medical Center

August 9, 2013

learning objectives
Learning objectives
  • Describe the roll of good intestinal flora
  • Identify the epidemiology and pathophysiology of Clostridiumdifficile
  • Recognize the risk factors for infection
  • Stratify the different categories of Clostridiumdifficile
  • Establish a treatment regimen for a patient with Clostridiumdifficile
history of present illness
History of present illness
  • Louis Bowel (LB) is a 64 yo male admitted for epistaxis on 6/19/13 with a life threatening bleed, later diagnosed with a stroke
  • He is discharged to the rehabilitation floor on 6/21/13 to undergo therapy
  • Upon transfer to rehabilitation he has diarrhea and severe abdominal pain
past medical history
Past medical history
  • COPD
  • H/O recurring epistaxis episodes since 2006
  • HTN
  • H/O falls resulting in rib fractures
  • BPH
  • Recent sinus infection positive for S. pneumonia
labs 6 19 13
Labs : 6/19/13








C. diff





physical exam 6 21 13
Physical exam: 6/21/13
  • Vitals:
    • BP – 167/106
    • RR – 34
    • Sat. Ox – 97% on O2
  • Abdomen
    • Soft, non-tender
    • Active bowel sounds
  • HR - 112
  • Temp – 36.4˚
physical exam 6 21 131
Physical exam: 6/21/13
  • Extremities:
    • 1+ RLE edema
  • Lungs:
    • Volume out is greater than volume in on both sides
    • Wheezing on exhale
social history
Social history
  • Alcohol abuse (750 ml/day of vodka)
  • 2 pack/year smoker (decreased in the last year)
  • Divorced, lives in an apartment alone His daughter lives in the same complex and will be able to assist in his care
  • No home medications were reported
  • Medications at time of transfer:
    • albuterol/ipratropium neb 4 times daily
    • multivitamin 1 tablet VFTdaily
    • pantoprazole 40 mg IV daily
    • vit. D3 2000 units VFTdaily
    • heparin 5000 units SQ tid
    • flonase 2 sprays each nostril daily
    • chlorhexadine 15 ml swish and suction tid
  • Before admission to the rehabilitation unit, LB was given imipenem X 7 days for a sinus infection. The exact dose and route of imipenem was not available
  • He was started on vancomycin 1000mg IV Q12h on 6/18/13 which was changed to Q8h on day 2 and then d/c on day 3
  • On 6/22/13, LB was started on amoxicillin/clavulanate VFT bid X 15 days for unresolved sinusitis

The human digestive tract is home to more than 500 species of microorganisms.

intestinal flora
Intestinal Flora
  • When healthy, this colonization is not only beneficial, but necessary to the host
  • Normal flora helps with digestion and absorption of nutrients as well as enhanced immunity from infectious agents



  • Normal flora protect the intestinal wall from pathogenic bacteria
  • Probiotics aren’t regulated by the FDA
  • Inconsistencies in products makes significant data hard to acquire
  • Meta-analysis showed benefit in C. diff prophylaxis. However, there were substantial data sets missing, so it is difficult to make a definitive conclusion as to how helpful this treatment would be
  • IDSA guidelines do not recommend using probiotics for C. difficile prophylaxis

Goldenburg JZ, et al. Cochrane. 2013; 5.

Cohen, S, et al. 2010 Shea-IDSA.

  • The incidence of Clostridium difficile Associated Diarrhea (CDAD) increased 2 fold from 1996 – 2003 (61 in 100,000)
  • Rates increased 10 fold in patients over the age of 65 (43 in 1,000)
  • New strains such as NAP1/BI/027 are more virulent and have higher resistance than their ancestors

Lamont J, et al. UpToDate2013 Jul 30

  • CDAD is more likely with new exposure, while previously exposed individuals are more likely to not develop symptoms
  • Clindamycin used to be known as the most likely antibiotic to cause C. difficile
  • Fluoroquinolones are emerging as the new perpetrator. The NAP1/BI/027 appears to be correlated to fluoroquinolone use

Lamont J, et al. UpToDate2013 Jul 30

risk factors
Risk factors
  • Antibiotic use
  • Hospitalization or long term care facility
  • Health care workers
  • Advanced age (>64)
  • Suppression of stomach acid (PPI)?
  • Chemotherapy
  • Gastrointestinal tract manipulation (including tube feeds)

Cohen, S, et al. 2010 Shea-IDSA

proton pump inhibitor ppi
Proton Pump Inhibitor (PPI)
  • In a 2011 study, it was determined that PPI use increases a patients risk for C. diff 2 fold
  • The study couldn’t show causation but in the meta-analysis that looked at 30 studies and over 200,000 patients, there was a strong correlation between PPI use and C. diff

Deshpande A, et al. Clinical Gastroenterology and Hepatology; 10(3). P 225-33

patient case1
Patient case

Which risk factors does LB have?

  • Recent antibiotic use
  • Long hospital stay
  • Tube feed
  • PPI use
  • Age? (64)
  • Colonization is facilitated through oral-fecal route
  • C. difficile releases two protein chain toxins: toxin A and toxin B
  • When these toxins gain intracellular entrance, they inhibit Rho protein facilitated regulatory pathways and lead to cell apoptosis

Cohen, S, et al. 2010 Shea-IDSA

  • Toxin A stimulates inflammation and initiates intestinal fluid secretion
  • Toxin B is responsible for the virulence of C. difficille and strains that lack toxin B will colonize without being pathogenic

Cohen, S, et al. 2010 Shea-IDSA


Cohen, S, et al. 2010 Shea-IDSA

  • Initial episode (mild to moderate)
    • Metronidazole 500 mg PO tid X 10 – 14 days
  • Initial episode (severe)
    • Vancomycin 125 mg PO four times daily X 10 – 14 days
  • Initial episode (severe complicated)
    • Vancomycin 500 mg PO (or NGFT) four times daily + metronidazole 500 mg IV Q8h

Cohen, S, et al. 2010 Shea-IDSA

  • First recurrence
    • Same treatment as initial episode
  • Second recurrence
    • Vancomycin in a tapered and/or pulsed regimen

Cohen, S, et al. 2010 Shea-IDSA

new options
New options
  • Fidaxomicin (Dificid®)
    • Macrolide that is minimally absorbed so there are minimal side effects
    • Dosed at 200 mg PO bid X 10 days
    • Very expensive ~ $270/day
    • Similar efficacy to vancomycin, but less recurrence
    • Not tested against metronidazole

Louie T, et al. NEJM. 2011

  • In a multi-center, randomized, double blind, non-inferiority trial, fidaxomicin 200 mg PO bid was compared to vancomycin 125 mg PO 4 times daily both for 10 days for treatment of C.diff
  • It was evaluated on both per-protocol and intention-to-treat populations. In both analyses fidaxomicin was found to not be inferior to vancomycin
  • Fidaxomicin was also found to have less recurrence

Louie T, et al. NEJM. 2011

  • Where is it’s place in therapy?
    • When the guidelines were published, fidaxomicin was not on the market
    • It has proven to be as effective as vancomycin, but the cost difference is drastic ($355/day for fidaxomycinvs$124.50/day for vancomycin)

Louie T, et al. NEJM. 2011

Red Book, 2013.

patient case2
Patient Case
  • LB was tested again for C. diff after being admitted to rehabilitation and tested positive on 6/21/13
patient case3
Patient case

Looking at LB’s labs, what is the proper classification for his disease?

patient case4
Patient case
  • LB was initiated on metronidazole 500 mg PO tid for 14 days on 6/22/13

Was this the appropriate regimen?


patient case5
Patient case
  • LB’s diarrhea and abdominal cramping persisted despite treatment. His labs were redrawn on 7/7/13. He was found to still be C. diff positive

What is LB’s level of severity now?





SCr = 0.42

patient case6
Patient Case
  • Metronidazole?
  • Vancomycin?
  • Fidaxomicin?
patient case7
Patient Case
  • LB was started on vancomycin 125 mg VFT Q6h for 14 days on 7/11/13
  • His route was changed to PO on 7/14/13
  • His dose was changed to 250 mg PO Q6h on 7/15/13
  • His diarrhea was resolving upon discharge on 7/24/13
review of c difficile
Review of C. difficile
  • Good bacteria are essential for nutrition and immune response
  • C. difficile is increasing in incidence
  • More virulent strains are being discovered, caused by resistance
  • Risk factors include:
    • Antibiotic use
    • Health care environments
    • Advancing age
    • PPI use?
  • Clinical Pharmacology [Internet]. Tampa, (FL): Gold Standard, Inc. fidaxomicin;[Updated 2013 Jul 15;Cited 2013 Aug 6]; [about 3 screens]. Available from: Registration and login required.
  • Louie T, Miller M, MullaneK, Shue Y, et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N Engl J Med [Internet]. 2011 [cited 2013 Aug 2]; 364:422-31.
  • LaMont JT. Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology.[Internet]. In: Calderwood S, Baron E, editors. UpToDate. Waltham (MA): UpToDate, Inc; 20103[cited 2013 Aug 3]. 4 p. Available from: Registration and login required.
  • Cohen S, Gerding D, Johnson S, Wilcox M, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Disease Society of America (IDSA). Infection Control and Hospital Epidemiology [Internet]. 2010 May[cited 2013 Aug 2];31(5):431-55. Available from: Registration and login required
  • Clostridium difficile [Internet]. Atlanta(GA): Centers for Disease Control and Prevention; 2013 [cited 2013 Aug 4]: Available from:

6. Deshpande A, Pant C, Pasupuleti V, Hernandez A, et al. Association

Between Proton Pump Inhibitor Therapy and Clostridium difficile Infection

in a Meta-Analysis. Clinical Gastroenterology and Hepatology [Internet].

2012 Mar [cited 2013 Aug 8]; 10(3):225-33.

7. Goldenberg JZ, Ma SSY, Saxton JD, Martzen MR, Vandvik PO, ThorlundK,

GuyattGH, Johnston BC. Probiotics for the prevention of Clostridium

difficile-associated diarrhea in adults and children. Cochrane Database of

Systematic Reviews 2013, Issue 5. Art. No.: CD006095. DOI:


8.  Micromedex 2.0 Red Book [Internet]. Greenwood Village (CO): Truven

Health Analytics Inc. c2013. fidaxomicin; [cited 2013 Aug 11]; [about 3

screens]. Available from: Registration

and login required.