Transcript Management of Clostridium difficile Infections

Management of
Clostridium difficile
Infections
U C I RV I NE ME DI CA L CE N TER
DE PA RTMENT OF I N T ERNAL ME DI CINE
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 14day 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.
B.
C.
D.
E.
Oral metronidazole for 14 days
Oral metronidazole taper over 42 days
Oral vancomycin for 14 days
Oral vancomycin plus parenteral metronidazole for 14 days
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.
2.
WBC ≥ 15,000
Abdominal tenderness
Complicated Disease
Any of the following attributable to CDI:
•
•
•
•
•
•
•
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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
o
Metronidazole (Flagyl) 500 mg orally 3 times a day for 10-14 days
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
o
o
o
•
Vancomycin 500 mg orally 4 times a day PLUS
Metronidazole 500 mg IV 3 times a day
CT abdomen recommended
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 regimen
o 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:
◦
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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.
B.
C.
D.
E.
Oral metronidazole for 14 days
Oral metronidazole taper over 42 days
Oral vancomycin for 14 days
Oral vancomycin plus parenteral metronidazole for 14 days
Oral vancomycin taper over 42 days
Case
Which of the following is the most appropriate treatment at this time?
A.
B.
C.
D.
E.
Oral metronidazole for 14 days
Oral metronidazole taper over 42 days
Oral vancomycin for 14 days
Oral vancomycin plus parenteral metronidazole for 14 days
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
References
Cohen 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>.