2. INTRODUCTION
Clostridium difficile infection (CDI)
• commonly diagnosed diarrheal illness acquired in the
hospital
• C. difficile that vegetate, multiply, and secrete toxins,
causing diarrhea and, in the most severe cases,
pseudomembranous colitis (PMC).
3. ETIOLOGY AND EPIDEMIOLOGY
C. difficile is an obligately anaerobic, gram-positive, spore-
forming bacillus
• Clindamycin, ampicillin, and cephalosporins were the
first antibiotics associated with CDI.
piperacillin/tazobactam pose significantly less risk.
• A few cases, especially in the community, are reported in
patients without documentation of prior antibiotic
exposure
4. ETIOLOGY AND EPIDEMIOLOGY
• The rate of fecal colonization increases in proportion to
length of hospital stay - ≥20% among adult patients
hospitalized for >2 weeks
• The incidence is higher among female patients,
Caucasians, and persons ≥65 years of age.
• Community-onset CDI without recent hospitalization,
accounts for ≤10% of all cases
5. RISK FACTORS FOR CDI
• risk factors for CDI include older age, greater severity of
underlying illness, gastrointestinal surgery, use of
electronic rectal thermometers, enteral tube feeding, and
antacid treatment.
• Use of proton pump inhibitors may be a risk factor, but
this risk is probably modest
6. PATHOLOGY AND PATHOGENESIS
toxin A (an enterotoxin) and toxin B (a cytotoxin)
• Disruption of the cytoskeleton results in loss of cell
shape, adherence, and tight junctions, with consequent
fluid leakage- pseudomembrane formation.
• third toxin, binary toxin CDT,this toxin is related to C.
perfringens
7. AUTOPSY SPECIMEN SHOWING CONFLUENT
PSEUDOMEMBRANES COVERING THE CECUM OF A
PATIENT WITH PSEUDOMEMBRANOUS COLITIS.
8. STUDIES
The whole colon is usually involved, but 10% of patients
have rectal sparing.
• four prospective studies have shown that colonized
patients who have not previously had CDI actually have
a decreased risk of CDI - colonized by nontoxigenic
strains.
• Two large clinical trials in which intravenous monoclonal
antibodies to toxin A and toxin B were used together
• Antibody to toxin A alone was ineffective.
9. CDI EVENTS
At least three events are integral to C. difficile
pathogenesis.1- Exposure to antibiotics establishes
susceptibility to infection. Once susceptible, the patient
may acquire nontoxigenic (nonpathogenic) or 2- toxigenic
strains of C. difficile as a second event.
Acquisition of toxigenic C. difficile may be followed by
asymptomatic colonization or CDI, including an
inadequate host IgG response to C. difficile toxin A.
10. INFANTS?
Infants are thought not to develop symptomatic CDI
because they lack suitable mucosal toxin receptors that
develop later in life.
11. CLINICAL MANIFESTATIONS
Diarrhea is the most common manifestation caused by C.
difficile.
• almost never grossly bloody ; watery or mucoid in
consistency, with a characteristic odor.
• fever in 28% of cases, abdominal pain in 22%, and
leukocytosis in 50%.
12. CLINICAL MANIFESTATIONS
• complications of C. difficile infection, particularly toxic
megacolon and sepsis.
• C. difficile diarrhea recurs after treatment in ~15–30% of
cases;
13. DIAGNOSIS
combination of clinical criteria:
(1) diarrhea (≥3 unformed stools per 24 h for ≥2 days) with
no other recognized cause plus (2) detection of toxin A or
B in the stool, detection of toxin-producing C. difficile in the
stool by nucleic acid amplification testing – ex. PCR
• visualized at endoscopy in only ~50% of patients with
diarrhea who have a positive stool culture and toxin
assay for C. difficile
14. DIAGNOSIS
negative result in this examination does not rule out CDI.
• Confirmation of the presence of toxin in the stool in
addition to PCR or glutamate dehydrogenase (GDH)
positivity is recommended in the European CDI
guidelines for diagnosis of CDI.
15. TREATMENT
When possible, discontinuation of any ongoing
antimicrobial administration
• General treatment guidelines include hydration and the
avoidance of antiperistaltic agents and opiates
• IV vancomycin is ineffective for CDI.
• Fidaxomicin is available only for oral administration.
16. TREATMENT
large clinical trials comparing vancomycin and fidaxomicin
indicated comparable clinical resolution of diarrhea in
~90% of patients
and the rate of recurrent CDI was significantly lower with
fidaxomicin.
• IV metronidazole is administered, fecal bactericidal drug
concentrations are achieved during acute diarrhea;
however, in the presence of adynamic ileus, IV
metronidazole treatment of CDI has failed.
17. TREATMENT
• study demonstrated the superiority of vancomycin over
metronidazole for treatment of severe CDI.
• vancomycin cure rate was superior to the metronidazole
• cure rate (81% vs 73% )
• All three drugs given for at least 10 days
18. RECURRENT CDI
~15–30% of successfully treated patients experience
recurrences of CDI
• lower in patients treated with fidaxomicin
• Recurrence rates are higher among patients ≥65 years
old, those who continue to take antibiotics
19. RECURRENT CDI
long or repeated metronidazole courses should be
avoided because of potential neurotoxicity.
• vancomycin in tapering doses or with pulsed dosing
every other day for 2–8 weeks may be the most practical
approach to treating patients with multiple recurrences.
20. RECURRENT CDI
• FDA-unapproved antibiotic strategies include (1)
sequential treatment with vancomycin (125 mg four
times daily for 10–14 days) followed by rifaximin (400 mg
twice daily for 14 days), (2) treatment with nitazoxanide
(500 mg twice daily for 10 days), and (3) vancomycin
(125 mg 4 times daily for 10 days) followed by
fidaxomicin (200 mg daily for 7 days, then every other
day for 13 doses).
21. SEVERE COMPLICATED OR FULMINANT
CDI
Fulminant (rapidly progressive and severe)
• Sepsis (hypotension, fever, tachycardia, leukocytosis)
• Cautious sigmoidoscopy or colonoscopy to visualize
PMC and an abdominal CT examination are the best
diagnostic tests in patients without diarrhea.
22. SEVERE COMPLICATED OR FULMINANT
CDI
The combination of vancomycin (given orally or via
nasogastric tube and by retention enema) plus IV
metronidazole has been used with some success in
uncontrolled studies
• IV tigecycline in small-scale uncontrolled studies.
• Surgical colectomy may be life-saving
23. SEVERE COMPLICATED OR FULMINANT
CDI
• mortality and morbidity associated with colectomy may
be reduced by performing instead a laparoscopic
ileostomy followed by colon lavage with polyethylene
glycol and vancomycin infusion into the colon via the
ileostomy.
25. Q1
Which of the following findings is unlikely to be found in C
difficile infection?
• A. Bloody diarrhea
• B. Fever
• C. Ileus
• D. Leukocytosis
• E. Recurrence after therapy
26. Q2
All of the following patients should be treated for C diicile infection EXCEPT:
• A. A 57-year-old nursing home resident with diarrhea for 2 weeks and
pseudomembranes found on colonoscopy with no evidence of toxin A or B in the
stool
• B. A 63-year-old woman with fever, leukocytosis, adynamic ileus, and a positive
PCR for C diicile
• in the stool
• C. A 68-year-old woman with recent course of antibiotics admitted to the medical
intensive care
• unit after presentation to the emergency department with abdominal pain and
diarrhea; she was
• found to have severe abdominal tenderness with absent bowel sounds,
systemic hypotension, and
• colonic wall thickening on CT of the abdomen
• D. A 75-year-old woman who completed therapy with amoxicillin for an upper
respiratory tract infection yesterday and now has had two loose bowel
movements per day for the last 3 days; she is afebrile and has a WBC count of
8600/μL
27. Q3
An 82-year-old woman with dementia has been living in a nursing
home for 5 years. She was
been seen by her primary care provider for evaluation of diarrhea 4
weeks ago. At that time, a stool
sample was positive by PCR for C difficile, and she was treated with
oral metronidazole with some
improvement in her symptoms. However, she has had five loose bowel
movements per day starting 4 days ago and now has abdominal
tenderness. Stool PCR remains positive. Which of the following is the
most appropriate therapy?
• A. Fecal microbiota transplantation
• B. Intravenous (IV) immunoglobulin
• C. Oral metronidazole
• D. Oral nitazoxanide
• E. Oral vancomycin
28. Q4
Which of the following antibiotics has the weakest
association with the development of C
difficile–associated disease?
• A. Ceftriaxone
• B. Ciproloxacin
• C. Clindamycin
• D. Moxiloxacin
• E. Piperacillin-tazobactam
Editor's Notes
#14:Lateral radiographic appearance of Pedro Pons' sign.
#25:D- Sulfonamides and tetracyclines are class D drugs. The speciic concern
for use of doxycycline in the second and third trimester is discoloration of the teeth in the fetus
#26:The most common presentation of C diicile infection is increased stooling, with stools
that may range from soft and unformed to profuse watery diarrhea. Stools are almost never
grossly bloody.
