Management of Clostridium difficile Infections UC IRVINE MEDICAL CENTER

DEPARTMENT OF INTERNAL MEDICINE

4/6/15

Objectives

1. What is Clostridium difficile infection (CDI) and how it’s diagnosed

2. Major risk factors for CDI

3. Define the severity of CDI

4. Treat CDI by degree of severity

5. Treat recurrent CDI

6. Examine alternative treatments

Case

42 year-old man is evaluated for recurrent diarrhea. Four weeks ago, the patient was diagnosed with a mild Clostridium difficile infection and treated with a 14-day course of metronidazole, 500 mg orally every 8 hours, with resolution of his symptoms. He currently takes no medications.

One week after his last dose of metronidazole, he again develops recurrent watery stools without fever or other symptoms. There is no visible blood or mucus in the stools.

Case

Physical examination findings are noncontributory.

Results of laboratory studies show a leukocyte count of 10,400/µL (10.4 × 109/L) and a normal serum creatinine level. A stool sample tests positive for occult blood, and results of a repeat stool assay are again positive for C. difficile toxin.

Case

Which of the following is the most appropriate treatment at this time?

A. Oral metronidazole for 14 daysB. Oral metronidazole taper over 42 daysC. Oral vancomycin for 14 daysD. Oral vancomycin plus parenteral metronidazole for 14 daysE. Oral vancomycin taper over 42 days

Introduction

• C. difficile is a gram positive, spore-forming bacterium that produces disease-causing toxins A&B

• PCR test for C. difficile toxin genes has high sensitivity and high specificity

• Repeat testing should be discouraged

• Testing for cure should not be done

Major Risk Factors

1. Antibiotic exposure

2. Organism exposure

3. Certain co-morbidities

4. GI tract surgery

5. Gastric acid reduction (e.g. PPI use)

CDI Disease Severity

Mild-to-Moderate Disease• Watery diarrhea (up to 10-15 times per day)

• Any additional signs or symptoms not meeting severe or complicated criteria

Severe Disease

Hypoalbuminemia (serum albumin <3 g/dl) plus ONE of the following:

1. WBC ≥ 15,0002. Abdominal tenderness

Complicated DiseaseAny of the following attributable to CDI:

• Admission to ICU • Hypotension with or without required use of vasopressors• Fever ≥ 38.5o C• Ileus or significant abdominal distension• Mental status changes• WBC ≥ 35,000 or <2,000• Lactate > 2.2• End organ failure (mechanical ventilation, renal failure, etc.)

Management of CDI• Mild-to-moderate disease:

o Metronidazole (Flagyl) 500 mg orally 3 times a day for 10-14 dayso If no improvement after 5-7 days, stop metronidazole and switch to vancomycin 125

mg orally 4 times a day for a total of 10-14 days

• Severe disease: vancomycin 125 mg orally 4 times a day for 10-14 days

Management of CDI• Complicated disease:

o Vancomycin 500 mg orally 4 times a day PLUSo Metronidazole 500 mg IV 3 times a dayo CT abdomen recommendedo Obtain surgical consult

• When oral antibiotics cannot reach a segment of the colon, add vancomycin 500 mg in 500 ml saline via enema 4 times a day until the patient improves

Recurrent CDI• 1st recurrence can be treated with the same regimen used for the initial

episode

• If 1st recurrence is severe, vancomycin should be used

• 2nd recurrence should be treated with a pulsed vancomycin regimeno Standard 10-day course of vancomycin (125 mg QID) o Then 125 mg daily pulsed every 3 days for 10 total doses

• For a 3rd recurrence after a pulsed vancomycin regimen, consider fecal microbiota transplant

Alternative Treatment Considerations

Fidaxomicin• Alternative treatment that can be used to for recurrent mild-to-moderate CDI

• Dose = 200mg PO BID x 10 days

• Demonstrated non-inferiority to vancomycin in 2 randomized control trials

• Drawbacks:◦ Significantly more expensive than vancomycin◦ Limited data on long-term efficacy

Probiotic Use• Saccharomyces boulardii did result in fewer recurrences in a group of patients

with recurrent CDI

• Caution:◦ Problems with study design◦ Limited use◦ Risk of bacteremia or fungemia◦ Use not recommended by guidelines

• Small trials of Lactobacillus use have failed to show efficacy in treating recurrent CDI

Now back to our case…

Case

In summary, 42 year-old male with a 1st recurrence of CDI.

He has mild-to-moderate disease.

Case

Which of the following is the most appropriate treatment at this time?

A. Oral metronidazole for 14 daysB. Oral metronidazole taper over 42 daysC. Oral vancomycin for 14 daysD. Oral vancomycin plus parenteral metronidazole for 14 daysE. Oral vancomycin taper over 42 days

Case

Which of the following is the most appropriate treatment at this time?

A. Oral metronidazole for 14 daysB. Oral metronidazole taper over 42 daysC. Oral vancomycin for 14 daysD. Oral vancomycin plus parenteral metronidazole for 14 daysE. Oral vancomycin taper over 42 days

Key Points• CDI is commonly encountered in the hospital

• Treatment is based on severity of infection (mild-moderate, severe, complicated)

• For mild-moderate CDI, if no improvement after 5-7 days of metronidazole, stop and switch to oral vancomycin

• For complicated CDI, add rectal vancomycin when oral antibiotics may not reach the colon

• Treat 1st recurrence with same regimen as initial infection

• Treat 2nd recurrence with pulsed vancomycin

• Treat 3rd recurrence with fecal transplant

• Currently probiotic use is not recommended by guidelines

The End

ReferencesCohen SH, Gerding DN, Johnson S, 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 diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31:431.

Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108:478.

Kelly, Ciaran P., MD, and J. Thomas Lamont, MD. "Clostridium Difficile in Adults: Treatment." Clostridium Difficile in Adults: Treatment. Ed. Stephen B. Calderwood and Elinor L. Baron. N.p., 31 Mar. 2015. <http://www.uptodate.com/contents/clostridium-difficile-in-adults-treatment?source=search_result&search=clostridium%2Bdifficile&selectedTitle=1~150#H10>.