Clostridium Difficile- Causative agent for Antibiotic associated diarrhea/Colitis.

Colonization of the intestinal tract occurs via the fecal-oral

route and is facilitated by disruption of normal intestinal flora
due to antimicrobial therapy.

The organism is capable of elaborating exotoxins that bind to

receptors on intestinal epithelial cells, leading to inflammation
and diarrhea.

RISK FACTORS-

Pathogenesis-

C Diff Recurrence
# Recurrence occurs in approximately 25% of successfully treated
patients either with metronidazole or vancomycin
# Following a second recurrence, subsequent episodes occur in as
many as 40%60% of patients
# Both metronidazole and vancomycin suppress the growth of the
normal microflora and thereby defeat natural colonization resistance

Cause of Recurrence
Persistence of C. difficile spores that germinate following
completion of therapy
Suppression or eradication of protective microflora
Establishment of newly acquired environmental spores
Failure of the host to establish an adequate immune
response to C. difficile toxins A and B
Germination of spores and relapse generally occur within
710 days of completion of antibiotic therapy
Mean time to reinfection from environmental sources has
been estimated at 42.5 days .

Current Guidelines
# First episode of non-severe uncomplicated CDI with oral metronidazole
500 mg TID for 1014 days .
# Oral vancomycin 125 mg QID daily for 1014 days has become the
standard for treating severe CDI.
# Treatment of the first recurrence of CDI is usually conducted with the same
regimen used to treat the initial episode, whereas tapered and/or pulsed doses of
vancomycin are recommended for second and subsequent recurrences.
# Tapering of Vancomycin 125 mg q 6 h10-14 days, 125 mg q 12h7 days,
125 mg q 24h7 days, 125 mg q 48-72 h2-8 weeks

Newer Treat. Altenative

ELIGIBILITY

Eligibility

Ages Eligible for Study:

16 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

ARMS of STUDY:

Active Comparator: vancomycin

Drug: Vancomycin125 mg capsules

q6hr (4 times a day)

Experimental: fidaxomicin

Drug: fidaxomicin200 mg capsules

q12hr (2 times a day)
Other Names:PAR-101
OPT-80
Dificid

CRITERIAInclusion Criteria:
- Males/females with CDAD
- Females must use adequate
contraception
- Signed informed consent

Exclusion Criteria:
- Life-threatening CDAD
- Toxic megacolon

OUTCOMEPrimary Outcome Measures:

Cure Rate at End of Therapy
[ Time Frame: Study day 10 (+/- 2 days) ]
# 3 or fewer unformed stools for 2
consecutive days and maintained through the end
of therapy
# no longer needed specific antiClostridium antibacterial treatment after completion
of the course of study medication.
Secondary Outcome Measures:

SAMPLESTUDY POPULATION-Patients with toxin-positive CDI

CDI Recurrence-

TIME to RECURRENCE

TimetorecurrencebytreatmentgroupinpatientswithapriorepisodeofClostridium
difficileinfection.

OliverA.Cornelyetal.ClinInfectDis.2012;55:S154-

Dispositionofpatients.

ANOTHER STUDY# risk for a second recurrence within 60 days

of diagnosis was similar whether patients
were treated with metronidazole, vancomycin,
or both for either the initial or first recurrent
episode .
# One-third of patients treated with either
antibiotic had a second recurrence, and risk
increased with age and duration of
hospitalization.