Enzyme Immunoassay (EIA) and Enzyme-Linked Immunosorbent
Assay (ELISA) were used by our institution and by referring
institutions for the detection of toxin A and/or B for the laboratory
confirmation of CDI until polymerase chain reaction (PCR) testing
became available in 2009. PCR has been the principal method for
toxin detection in our hospitals since shortly after its introduction.
Since PCR is far more sensitive that EIA/ELISA, we suspect that
patients diagnosed by enzymatic testing may have had later stage
CDI (they may have been sicker) than patients diagnosed by the
more sensitive PCR. However, the majority of the cases reported in
this series were diagnosed prior to the availability of PCR, and many
patients were referred to our institution from other facilities, where
confirmation of laboratory methods was not always possible.
Accordingly, we were not able to assess whether the outcomes from
FMT differ for patients initially diagnosed by different methods.
Gough et al. recently reviewed the efficacy of intestinal microbiota
transplantation (fecal bacteriotherapy) for RCDI, and reported
an overall cure rate of 92% [20]. Characteristics that were associated
with lower rates of resolution of diarrhea included single stool
sample instillation and instillation via the upper intestinal tract as
opposed to instillation into the lower intestinal tract using retention
enema kits or the colonoscope. In the current case series, 59 of 75
FMTcourses resulted in clinical resolution of recurrent diarrhea, for
a primary cure rate of 79%, which is essentially identical to the cure
rate reported in Gough’s review (77% when stool was administered
to patients via gastroscope or nasojejunal tube). When FMT is
provided through the lower GI tract (via a colonoscope or fecal
enema kit) the observed cure rates are higher and range between 92
and 98% [20,22]. Thus, the instillation route of FMT is important, not
only because of different success rates associated with different
routes of administration, but also because patient or provider
preferences may influence choice of routes of administration. The
explanation for the reported lower cure rates associated with FMT
administered via the upper gastrointestinal tract is not well
understood, but may simply be related to the lower volume of stool
mixture that has been used with the upper GI instillation procedure.
Additional research is needed on both the route of administration of
FMT and on the volume of stool mixture used.
The mechanism of action of stool transplantation has not been
established. However, patients with recurrent C. difficile infection
have been found to have decreased diversity in their stool microbiome
[25,26]. Ordinarily, C. difficile growth is inhibited by a normal
stool microbiome, but a depleted microbiome is thought to provide
an opportunity for C. difficile overgrowth. By repopulating the
gastrointestinal tract with a healthy microbiome, stool transplantation
appears to reestablish resistance to C. difficile growth,
often called colonization resistance [16]. To confirm the association
between stool transplantation and microbiome diversity, future
studies should examine the microbiome of patients with RCDI
before and after transplantation. Interestingly, we as well as others
[22] noted that patients who experience a relapse of CDI following
FMT have a high likelihood of responding to a standard treatment
course of vancomycin, which may be explained by a partial reestablishment
of a healthy stool microbiome diversity afforded by the
prior stool transplantation.