Vancomycin for the Treatment of NAAT(+)/Toxin(-) C. Difficile
Vancomycin for the Treatment of NAAT(+)/Toxin(-) C. Difficile
This study proposes to:

 1. Characterize the impact of oral vancomycin on C. difficile loads after end of treatment
 compared to a placebo group.

 2. Determine the effect of oral vancomycin on structural and functional microbiome changes
 after end of treatment compared to a placebo group.

 3. Characterize the impact of oral vancomycin against a placebo group on the daily
 frequency of loose stools by the end of treatment.
Clostridium difficile infection (CDI) is considered the most frequent healthcare associated
 infection in the US, causing almost half a million cases per year with an estimated annual
 cost of 4.8 billion dollars. Despite the existence of a few treatment options against CDI,
 yearly attributable deaths are estimated at 29,300 in the US. From April 2014 to April 2016,
 Froedtert Health reported 899 CDIs. Over half of these events are NAAT (Nucleic Acid
 Amplification Test)(+)/EIA (Enzyme immunoassay)(-) events. To test for CDI, NAAT followed by
 EIA is used in a Multistep algorithmic testing in which a sensitive nucleic acid
 amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay
 (EIA) and are among the most accurate methods for Clostridium difficile infection (CDI)
 diagnosis. There is currently uncertainty on how to treat these CDI events.

 The primary outcome of this randomized double blind controlled intervention trial will be
 changes in C. difficile (Clostridium difficile) loads between day 1 and day 14 and changes in
 C. difficile load between day 14 and day 28. Thirty patients with documented C. difficile
 will be randomized to either 14 days of vancomycin or placebo capsules. Block randomization
 will be used to assign patients to the treatment or placebo arms. Randomized assignments will
 be placed in sealed envelopes which will only be handled by the research pharmacist. Study
 related stool collections will be obtained on days 1, 7, 14, 21, and 28 (+/- 2days) [Day
 1=first day study drug was administered]. Patients will be followed for 90 days starting on
 day 1. Patients unable to complete at least 7 days of study treatment will be removed from
 analysis and replaced.
Inclusion Criteria:

 -  Must be at least 18 years of age at time of consent.

 -  Presence of loose stools triggering clinical C. difficile NAAT/toxin EIA testing.

 -  Having both C. difficile NAAT (+) and C. difficile toxin EIA (-).

 -  Admitted outside the hematology-oncology unit.

 -  Must be willing to keep a study supplied drug diary

 Exclusion Criteria:

 -  Presence of sepsis. Sepsis will be defined as a Sequential [Sepsis-related] Organ
 Failure Assessment (SOFA) score of 2 points or more as per 2016 definitions.

 -  Inability to take oral medications.

 -  Unwillingness or inability to provide written informed consent.

 -  Has a documented allergy to vancomycin.

 -  Has a documented life expectancy shorter than treatment course (14 days).

 -  Unwilling or unable to collect stool samples in the outpatient setting after
 discharge.

 -  Diagnosis of C. difficile colitis [NAAT(+) and toxin EIA(+)] in the preceding 3 months
 from enrollment.

 -  Received oral vancomycin during their current hospitalization, excluding empiric
 treatment given while pending C. difficile NAAT/toxin EIA results. Intravenous
 vancomycin is not an exclusion criterion.

 -  Women known to be pregnant or lactating during the study.