Clostridium

difficile
Infection
Consultants:
Dale N. Gerding, MD
Stuart B. Johnson, MD
Infectious Disease Division
Department of Medicine
Loyola University Chicago Stritch School of Medicine

Key Points

Diagnosis and Assessment

Selecting a Treatment Regimen

GuidelineCentral.com
 Key
Key Points
Points

C. difficile is the most common identifiable cause of antibiotic

associated diarrhea.*

C. difficile is an opportunistic organism which typically produces

two potent toxins, toxin A and toxin B. Some strains produce only
toxin B, and some strains also produce a third, unrelated toxin
(binary toxin). The role of binary toxin is uncertain and is not
identified by most clinical diagnostic tests.

The discovery of C. difficile strains (initially in North America

and subsequently Europe) that have increased virulence has
emphasized the need for effective diagnostic and control
measures.*

The clinical manifestations of infection with toxin-producing

strains of C. difficile range from symptomless carriage, to
mild or moderate diarrhea, to fulminant and sometimes fatal
pseudomembranous colitis.

A case definition of Clostridium difficile infection (CDI) should

include the presence of symptoms (usually diarrhea) and either a
positive stool test for C. difficile toxins or toxigenic C. difficile, or
direct visualization revealing pseudomembranous colitis.

A history of treatment with antimicrobial or antineoplastic agents

within the previous 8 weeks is present in the majority of patients.

Rarely (< 1%), a symptomatic patient will present with ileus and
colonic distension with minimal or no diarrhea.

*http://www.rapidmicrobiology.com/test-methods/Clostridium-difficile.php

Prevention
Minimize frequency, duration and number of antimicrobial agents
prescribed to reduce CDI risk (A-II).

Implement an antimicrobial stewardship program (A-II).

>> Antimicrobials to be targeted should be based on local epidemiology and the strains
present, but cephalosporin and clindamycin restriction (excluding surgical antibiotic
prophylaxis) may be particularly useful (C-III).
No recommendations can be made regarding prevention of
recurrent CDI in patients requiring continued antimicrobial
therapy for an underlying infection (C-III).
 Diagnosis and Assessment

Stool culture is the most sensitive test and is essential for

epidemiological studies (A-II).

Testing for C. difficile or its toxins should be performed only

on diarrheal (unformed) stool unless ileus due to C. difficile is
suspected (B-II).

Testing of stools of asymptomatic patients, including use as a

test of cure, is not recommended except for epidemiological
studies (B-III).

Enzyme immunoassay (EIA) testing for toxin A and B is rapid but is

less sensitive than the cell cytotoxin assay and is thus a sub-optimal
alternative approach for diagnosis (B-II).
>> Comment: One potential strategy to overcome this problem is a two-step method
using EIA for glutamate dehydrogenase (GDH) as an initial screen and the cell
cytotoxicity assay or toxigenic culture as the confirmatory test only on GDH
positive stools. This approach remains an interim recommendation (B-II).
Polymerase chain reaction (PCR) testing appears to be rapid,
sensitive and specific and may ultimately address testing concerns.
More data on utility are necessary before this methodology can be
recommended for routine testing (B-II).

Repeat testing during the same episode of diarrhea is of limited

value and should be discouraged (B-II).

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 Selecting a Treatment Regimen

Discontinue inciting antimicrobials as soon as possible since this

may influence the risk of CDI recurrence (A-II).

If possible, avoid antiperistaltic agents since they may obscure

symptoms and precipitate toxic megacolon (C-III).

Metronidazole is the drug of choice for the initial episode of

mild-moderate CDI.
>> The dose is 500 mg orally tid for 10-14 days (A-I).
Vancomycin is the drug of choice for an initial episode of severe
CDI.
>> The dose is 125 mg orally qid for 10-14 days (B-I).
Vancomycin orally (and per rectum if ileus is present) with
or without metronidazole IV is the regimen of choice for the
treatment of severe, complicated CDI.
>> Vancomycin is dosed at 500 mg qid orally and 500 mg in ~100 mL NS q6h
retention enema. Metronidazole is given at 500 mg q8h IV (C-III).
Consider colectomy in severely ill patients.
>> Monitoring serum lactate and peripheral white blood cell (WBC) count may be
helpful in prompting a decision to operate since serum lactate rising to 5 mmol/L
and WBC rising to 50,000 per mL have been associated with greatly increased
peri-operative mortality. If surgical management is necessary, carry out a sub-total
colectomy with preservation of the rectum (B-II).
Treatment of the first recurrence is usually with the same
regimen as for the initial episode (A-II) but should be stratified
by disease severity (mild to moderate, severe or severe/complicated)
as is recommended for treatment of the initial CDI episode (C-III).

Do not use metronidazole beyond first recurrence or for

long-term chronic therapy due to potential for cumulative
neurotoxicity (B-II).

Treatment of the second or later recurrence with vancomycin

using a taper and/or pulse regimen is the preferred next
strategy (B-III).

Probiotics
Currently available probiotics are not recommended to prevent
primary CDI since there are limited data to support this approach,
and there is a potential risk of blood stream infection (C-III).

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 Clostridium difficile Infection

Initial Episode

Mild or Moderate Severe Complicated

Leukocytosis < 15,000 and Leukocytosis 15,000 or creatinine Hypotension or shock, ileus,
creatinine < 1.5X pre-morbid level 1.5X pre-morbid level megacolon

A-I B-I C-III

Metronidazole PO Vancomycin PO Vancomycin

500 mg tid for 10-14 days 125 mg qid for 10-14 days 500 qid PO or via NG tube plus
metronidazole IV 500 mg q8h

1st Recurrence
If complete ileus:
consider adding rectal instillation of
A-II vancomycin

Same as for initial episode

2nd Recurrence

B-III

Vancomycin, tapered/pulsed

Drugs for Oral Therapy

Agent How Supplied Side Effects
Metronidazole 250 mg Common: nausea, headache, anorexia,
500 mg vomiting, diarrhea, epigastric distress,
abdominal cramping, constipation
Serious: convulsive seizures, peripheral
neuropathy
Vancomycin 125 mg & 250 mg capsules Extremely rare with oral use
Alternative: 500 mg/100 mL;
1 g/200 mL liquid

Recommendations for the Treatment of Clostridium difficile Infection

Clinical Supportive Recommended
Definition Clinical Data Treatment
Initial episode, mild Leukocytosis < 15,000 and Metronidazole 500 mg PO tid
or moderate creatinine < 1.5X pre-morbid level for 10-14 days
Initial episode, Leukocytosis 15,000 or Vancomycin 125 mg PO qid
severe creatinine 1.5X pre-morbid level for 10-14 days
Initial episode, Hypotension or shock, Vancomycin 500 mg qid PO or via NG
complicated ileus, megacolon tube, plus IV metronidazole 500 mg q8h
If complete ileus: consider adding rectal
instillation of vancomycin
First recurrence Same as for initial episode
Second recurrence Vancomycin, tapered/pulsed

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 Summary of Infection Control Measures for the Prevention of Horizontal
Transmission of Clostridium difficile
Strength of
Recommendation
Hand Hygiene A-II
Contact Precautions
a. Glove use A-I
b. Gowns B-III
Private Room or Cohorting C-III
Environmental cleaning, disinfection, or use of disposables
a. Replace electronic rectal thermometers with disposables B-II
b. Use of hypochlorite (1000-5000 ppm) for disinfection if CDI rates B-II
are increased

Strength of Recommendation and Quality of Evidence

Category/Grade Definition
Strength of Recommendation
A Good evidence to support a recommendation for or against use.
B Moderate evidence to support a recommendation for or against use.
C Poor evidence to support a recommendation.
Quality of Evidence
I Evidence from 1 properly randomized, controlled trial.
II Evidence from 1 well-designed clinical trial, without randomization; from
cohort or case-controlled analytic studies (preferably from > 1 center); from
multiple time-series; or from dramatic results from uncontrolled experiments.
III Evidence from opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees.
Abbreviations
CDI, Clostridium difficile infection; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; IV,
intravenous; NG, nasogastric; NS, normal saline; PCR, polymerase chain reaction; WBC, white blood cell
Source
Cohen SH, Gerding DN, Johnson SB, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH. 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(5):431-55.
Disclaimer
This Guideline attempts to define principles of practice that should produce high-quality patient care. It focuses
on the needs of primary care practice, but also is applicable to providers at all levels.
This Guideline should not be considered exclusive of other methods of care reasonably directed at obtaining the
same results. The ultimate judgment concerning the propriety of any course of conduct must be made by the
clinician after consideration of each individual patient situation.
Neither IGC, the medical associations, nor the authors endorse any product or service associated with the distributor
of this clinical reference tool.

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