Hindawi Publishing Corporation
Gastroenterology Research and Practice
Volume 2011, Article ID 136064, 11 pages
Inflammatory BowelDisease:A Review
Division of Gastroenterology, Feinberg School of Medicine, Northwestern University,
676 N St Clair Street, Suite 1400, Chicago, IL 60611, USA
Correspondence should be addressed to Preetika Sinh, email@example.com
Received 27 February 2011; Revised 17 June 2011; Accepted 5 July 2011
Academic Editor: Genevieve B. Melton-Meaux
Copyright © 2011 Preetika Sinh et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The incidence of Clostridium difficile infection (CDI) has significantly increased in the last decade in the United States adding to
the health care burden of the country. Patients with inflammatory bowel disease (IBD) have a higher prevalence of CDI and worse
it is not uncommon to diagnose CDI in a pregnant women or young adult who has no risk factors. C. difficile can be detected at
the initial presentation of IBD, during a relapse or in asymptomatic carriers. It is important to keep a high index of suspicion for
CDI in IBD patients and initiate prompt treatment to minimize complications. We summarize here the changing epidemiology,
pathogenesis, risk factors, clinical features, and treatment of CDI in IBD.
ized patients, or those with a history of antibiotic exposure
[1, 2]. The trend has changed with increasing numbers of
acquiring CDI [3, 4]. Patients with inflammatory bowel
diseases (IBD), ulcerative colitis (UC), and Crohn’s disease
(CD) are also acquiring CDI in increasing numbers and have
worse outcomes with higher rates of hospitalization, surgery,
and mortality as compared to non-IBD CDI patients [5–7].
The recognition of a new hypervirulent strain of Clostridium
difficile called NAP1/B1/027 has been linked to the increase
in health care burden in the last 10 years. The annual health
care cost of C. difficile infection (CDI) in the United States
is between $436 million to $3 billion according to published
data in the last decade [8–11].
The role of C. difficile in antibiotic associated diarrhea and
pseudomembranous colitis was first described in the late
1970’s [12, 13]. A number of studies have reported a higher
prevalence of CDI in IBD patients [5–7, 14, 15]. Cases of
C. difficile among UC patients reported in a nation wide
data analysis by Nguyen et al. between 1998 and 2004 were
3.73% as compared to 1.09% for Crohn’s disease and 0.45%
for general inpatient admissions. They also found that the
incidence of CDI in UC patients had doubled from 2.66%
to 5.12% over those 7 years . A study based on a
larger cohort of IBD patients in the United States reported
similar results and found that CDI was more common in
UC patients (2.8%) as compared to the general inpatient
population (0.4%) . There was no significant increase in
the overall prevalence of CDI in all Crohn’s disease patients
over the study period (1993–2003), but there was an increase
in cases of CDI in CD patients with large bowel disease from
1.22% to 2.31% . Rodemann et al. around the same time
period (1998–2004) reported adjusted odds ratio of all IBD,
UC, and CD admission with CDI as 2.9 (95% CI, 2.1–4.1),
with doubling of CDI admissions in patients with CD and
tripling in those with UC . More recent data from a
retrospective observational study by Issa et al. found that the
rate of CDI in IBD patients increased from 1.8% in 2004 to
4.6% in 2005. The majority of cases reported in 2005 were
2 Gastroenterology Research and Practice
. It was argued by Powell et al. that the relative increase in
CDI in UC compared to CD was due to the extent of colonic
involvement in UC rather than the difference in nature of the
two diseases . Their preliminary data suggests a much
higher incidence of CDI in left sided and extensive disease
as compared to distal disease. Hence, the incidence of CDI
has not only increased in the general population but also to a
greater extent in IBD patients.
3.Pathogenicityof C. difficile
C. difficile spores are transmitted by fecal-oral route, which
when ingested find an adequate environment and pH
in the bile of the small bowel to germinate into their
vegetative forms and subsequently colonize the intestine.
Toxin-induced damage of the mucosal barrier is the main
pathogenic mechanism of C. difficile. Two main types of
toxins, namely, toxin A and toxin B are important for
pathogenesis. Both have the ability to be enterotoxic and
cytotoxic though traditionally toxin A is considered entero-
toxic which causes disruption of the intestinal epithelial
lining giving way to cytotoxic toxin B . This leads to
activation of a cascade of proinflammatory cytokines and
leukotrienes like tumor necrosis factor (TNF), interleukin
(IL)-6, IL-8, IL-1β, leukotrienes B4, and interferon-γ [18,
19]. These cytokines account for enhanced permeability,
diarrhea, epithelial apoptosis, and ulceration.
Genes encoding toxin A (tcdA) and toxin B (tcdB) can
be upregulated (tcdR) or downregulated (tcdC) by genes in
the same loci. The local effect of these toxins is mediated by
internalization of toxin via an endosome in epithelial cells
leading to a sequence of conformational changes that release
the TcdB toxins catalytic-DXD glycosyltransferase domain.
Subsequent glycosylation of the target RhoGTPase disrupts
the cellular cytoskeleton and causes cell death [20–22].
Most strains of C. difficile produce both toxin A and
B. The proinflammatory mediators induced by these toxins
are responsible for the formation of pseudomembrane. It is
interesting to note that the classical pseudomembrane is not
a frequent finding in IBD-associated CDI . One possible
explanation is that the weakened intestinal lymphoepithelial
environment of a chronically active IBD patient is unable
to mount an adequate inflammatory response to form
a pseudomembrane. Immunomodulating drugs may also
contribute by altering mucosal inflammatory responses. A
third toxin called binary toxin is produced by some strains
though the exact role is not well understood .
The emergence of a hypervirulent strain NAP1/B1/027
at the beginning of the last decade coincided with the
increase in CDI cases . In early 2000, an atypical strain
that was group B1 (restriction-endonuclease analysis REA),
type NAP1 (North American PFGE type 1) and ribotype
027 (polymerase chain reaction PCR) was isolated from
outbreaks and found to exhibit hypervirulent features that
caused more severe disease .
Table 1: Risk factors for Clostridium difficile infection in IBD.
(i) More common
(3) Broad spectrum penicillin
(4) Broad spectrum cephalosporins
(ii) Less common
(b) Corticosteroid use
(2) Disease related:
(a) Disease subtype: ulcerative colitis versus Crohn’s disease
(b) Colonic involvement in IBD
(3) Hospitalization and exposure to hospital personnel
(4) Nonsummer months (20% higher rate)
(5) Advanced age
(6) Residence at long-term care facility
The atypical NAP1/B1/027 strain has several features
that contribute to its clinical presentation. It is resistant
to fluoroquinolones. It has mutated tcdC that negatively
regulates tcdA and tcdB. It produces 16 and 23 times more
TcdA and TcdB as compared to the common toxinotype 0
strains in vivo. It produces a third toxin called binary toxin
whose function in CDI is unclear. This strain is a toxinotype
III as compared to most other strains that are toxinotype
0 . Toxinotyping is based on pathogenic gene loci in
bacteria that carry genes encoding the toxins.
Risk factors associated with CDI in the general popula-
tion are antibiotic use, older age, residence in long-term
care facilities, hospitalization, immunosuppression, greater
comorbid burden, cancer, gastrointestinal disorders, and
gastrointestinal surgery (Table 1). In 2005, the Centers for
Disease Control (CDC) reported cases of fatal CDI in young
and peripartum patients who had no prior exposure to
antibiotics or medical facilities. These patient groups were
not thought to be the typical at-risk population .
Risk factors in IBD patients include older age, antibiotic
use, steroids, greater comorbid burden, and those with
colonic disease. Increasing age in IBD patients has been
shown to be a risk factor for CDI [9, 27, 28], although
IBD patients with CDI tend to be younger than those
with CDI in the general population. Antibiotic use alters
the normal bacterial flora and can lead to CDI [29–31].
Broad-spectrum antibiotics are more likely to cause CDI
primarily because of a greater disruption of the normal
microflora. Nearly all antibiotics have been reported to
cause CDI even those with therapeutic properties (e.g.,
metronidazole and vancomycin) . Clindamycin was one
of the initial culprits, but more recent outbreaks of CDI
Gastroenterology Research and Practice3
tend to be associated with broad-spectrum antibiotics like
fluoroquinolones. These case reports emerged with the
reporting of the NAP1/B1/027 strain that is resistant to this
drug [33, 34]. Antibiotic exposure is an important factor
altering host microbiota and most of the studies show an
exposure rate close to 60% in IBD patients with CDI [6, 35].
Even though antibiotic exposure is an important risk factor
for CDI in IBD, the absence of it should not lower the
suspicion of CDI.
Immunosuppression is a risk factor for CDI. Immunosup-
pression with corticosteroids has been associated with CDI
in IBD patients. A study of IBD patients in British Columbia
between 2001 and 2006 showed a threefold increase in risk of
CDI with corticosteroid use, with or without immunomod-
ulators therapy (RR 3.3 95% CI 1.88–6.10) . It is not
clear if the immunomodulating drugs like azathioprine, 6-
mercaptopurine, and methotrexate enhance the risk of CDI.
Issa et al. reported in their single tertiary center study an
odds ratio of 2.56 (P = 0.011 95% CI 1.28–5.12) for CDI
for patients on maintenance immunosuppression. There was
a greater risk with purine analogs (i.e., azathioprine or 6-
mercaptopurine) with or without infliximab . However,
a recent observational study of CDI in IBD patients found
no association between immunomodulators and the risk of
CDI, emphasizing the need for more research in this area
. Thus far, there is no evidence from these retrospective
studies that biological agents like infliximab are associated
with an increase risk of CDI. In addition, those IBD patients
with greater comorbid burden are at increased risk for
CDI. Nguyen et al. found a 13% increase in risk of CDI
with each 1-point increase in the Charlson’s comorbidity
burden index . Studies examining the association of
proton pump inhibitor (PPI) use and CDI in the general
population have shown conflicting results and more data
is needed with regards to the IBD population [33, 38–43].
Larger prospective studies will be needed to better define this
6.Presentationof C. difficile InfectioninIBD
6.1. Clinical Features and Outcome. An episode of CDI is
characterized by increase in stool frequency, diarrhea, fever,
nausea, abdominal pain, and tenderness with nonbloody
stools. The presentation can range from asymptomatic
carriage to severe infection with toxic megacolon and ileus
requiring surgical intervention . C. difficile in IBD
may show atypical features like frequent bloody stools and
presentation in younger patients with no prior exposure
to hospital facility [6, 45]. It is important to keep a high
suspicion for CDI in these patients. Even in the absence of
diarrhea if constitutional symptoms and laboratory findings
like leukocytosis with left shift are indicative of a possible
infectious source, it is prudent to rule out C. difficile. Articles
highlighting the role of CDI in IBD flares were published as
early as the 1980’s [46–49], but there was no clear consensus
onchecking C.difficile toxin inIBDflare[46–52]until recent
data by Meyer et al. and others emphasized the importance
of C. difficile during IBD relapse [5–7, 53–55].
CDI worsens IBD outcome. IBD patients with CDI have
higher rates of inpatient endoscopy and surgical procedures,
longer length of hospital stay, and higher mortality as
compared to non-CDI IBD or CDI-only patients [5, 6].
In a single center study at the University of Wisconsin in
2004-2005, more than half of the infected IBD patients
required hospitalization and 20% required colectomy .
Another single center study analyzed the outcome of UC
patients with and without CDI over a period of one year.
The investigators found significantly more hospitalizations
(58% versus 27%) and higher rates of colectomy (44.6%
versus 25%) in C. difficile positive- as compared to C. difficile
negative-UC patients in the follow-up year. Differences in
the colectomy rates and the lengths of hospital stay at initial
admission were not statistically significant . However,
data analyzed by Anathakrishnan et al. from a nationwide
inpatient sample (2003) showed that hospital stays were
three-day longer in C. difficile positive subjects. The CDI
and IBD group was six times more likely to undergo bowel
surgery than the C. difficile-only group and had four times
higher mortality than patients admitted to the hospital with
IBD alone or C. difficile alone. The endoscopy and surgical
rates in UC were higher than CD . A recent retrospective
IBD cases showed that CDI does not increase the risk of
colectomy in UC patients at 3 month followup . A
negative relationship between colectomy and CDI was also
observed by Nguyen et al. in their nationwide survey of
inpatients from 1998 to 2004 . The improved outcome
could be attributed to prompt pathogen-directed treatment
for C. difficile infection in UC subjects . This result
in IBD patient with CDI than those without [5, 6]. Prospec-
tive studies need to be conducted to better address this
Not only does CDI add to the morbidity and health
care cost due to longer hospital stays and higher number
of procedures, it also contributes to a higher case fatality
rate in IBD patients (5.7%–18% in IBD and CDI versus.
1.4%–2.1% in IBD alone) . The effect of CDI on CD
is less pronounced as compared to UC. This may be due to
less colonic Crohn’s in the population studied and possibly
higher use of metronidazole in CD [15, 56]. Even in studies
that showed no increase in colectomy rates in C. difficile
cases the mortality was higher as compared to non-IBD
cases  arguing that there are other variables at play.
Stratification of study patients based on disease severity and
use of immunomodulators may help find answers to these
When comparing data, it is prudent to keep in mind the
variability of testing for C. difficile colitis in various centers.
Nevertheless, it is clear that CDI is detrimental to the clinical
outcome of an IBD patient, already complicated by reduced
host immunity from drugs, malnutrition, and physical stress
(from surgery, infection, bleeding, etc.).
Small bowel CDI has been reported only in postcolec-
tomy IBD patients. High ileostomy output accompanied
by abdominal tenderness, nausea, fever, and high leukocyte
count are the usual presenting complaints . There have
4Gastroenterology Research and Practice
also been case reports of C. difficile causing diversion colitis
and pouchitis in postcolectomy cases [58–61].
6.2. Endoscopic Findings. The endoscopic finding of pseu-
domembranes found in 50% of C. difficile infected patients
(according to data from last decade), is less common
(13%)  in IBD patients with CDI [6, 63, 64]. Pseu-
domembrane formation occurs when there is disruption of
cellular cytoskeleton by toxins leading to ulcer formation.
These ulcers leak out serum proteins, inflammatory cells,
and mucus forming plaques on the colonic mucosa that
cannot be removed by lavage . Although IBD patients
with pseudomembranes present more commonly with fever
their clinical outcome is similar to patients without pseu-
domembranes, . Other endoscopic features of CDI in
IBD patients are nonspecific findings of edema, erythema,
friability, and inflammation of the colonic mucosa .
Anaerobic stool culture is the most sensitive test for diag-
nosing C. difficile, but it is labor intensive and has a turn
around time of 48 hours. The cytotoxin assay test, which
has a sensitivity of 67–100%, also requires 24–48 hours .
A combination of stool culture followed by identification of
toxigenic culture is recommended as the standard for clinical
On the other hand, enzyme immunoassay (EIA) for
toxins A and B is rapid and more commonly used. The
sensitivity of single sample testing is low (72%) [6, 67]
and may increase by 10% with second stool testing (84%)
. Peterson et al. reported a sensitivity of 86% with
three sample testing . Although three sample testing
increases the yield of EIA for C. difficile toxin detection
it adds to the health care cost of the disease. Infectious
Diseases Society of America (IDSA) does not recommend
repeat testing during the same episode . Binion et al.
at the Medical College of Wisconsin found that in IBD
patients the sensitivity is even less impressive (54%). With
a second, third, and fourth specimen, it increases to 75%,
78%, and 92%, respectively . The specificity and negative
predictive values of this test are 98% each . More data is
awaited on newer testing modalities like real-time PCR that
are rapid and sensitive. PCR has sensitivity and specificity
of 86–100% and 93–98%, respectively . The IDSA does
acknowledge that there is no testing strategy that is optimally
sensitive and specific. An interim recommendation made in
the 2010 guidelines suggests using a two-step method that
uses EIA detection of glutamate dehyrogenase (GDH) as
the initial screening test followed by cellcytotoxicity assay
or toxigenic culture for confirmation. At our institution all
stool samples are screened with EIA for GDH. Toxin assay
(EIA) is run on GDH-positive specimens. GDH-positive,
toxin-negative samples are cultured for C. difficile isolates.
Recovered isolated are cultured in broth to test for the
production of toxin. More research needs to be done to
determine the optimal diagnostic test for CDI in the general
population as well as in IBD patients.
Table 2: Treatment of Clostridium difficile infection: IDSA guide-
Initial episode, mild
to moderate disease
Initial episode, severe
Metronidazole 500mg three times a
day by mouth for 10–14 days
Vancomycin 125mg four times a
day by mouth for 10–14 days
Vancomycin, 500mg four times a
day by mouth or by nasogastric
tube, plus metronidazole, 500mg
every 8 hours intravenously. If
complete Ileus, consider rectal
instillation of vancomycin
Same as for initial episode
Vancomycin in a tapered and/or
Initial episode, severe
∗Severe uncomplicated infection: white blood cell count of 15,000cells/μL
or higher or serum creatinine level greater than or equal to 1.5 times the
premorbid level. Severe complicated infection: hypotension or shock, ileus,
megacolon (classification based on expert opinion by Infectious disease
society of America (IDSA) .
Endoscopy is not considered diagnostic for CDI. Non-
specific findings on endoscopy are common in IBD-related
CDI, but stool samples sent during colonoscopy can be
It is important for the physician to keep a high index of
suspicion for CDI in IBD patients. Stool tests should also be
performed in cases of IBD relapse, especially with a history
of antibiotic use in the last couple of months .
It is important to keep a high index of suspicion followed by
prompt diagnosis and early treatment of C. difficile in IBD
patients. In IBD local host defenses could be compromised
due to altered gut microflora from the disease or concurrent
use of immunomodulators making management challeng-
ing. Secondly, the symptoms and endoscopic appearance
of active CD or UC are very similar to CDI. Thus, CDI
Immunomodulators (including corticosteroids) treat IBD
flares but could be detrimental for CDI  (Table 2).
8.1. Antibiotics. Metronidazole is the first line of treatment
for mild-to-moderate CDI even though it is not FDA
approved for this indication. The typical dose for mild-
to-moderate CDI is 500mg orally three times a day for
10−14 days. Metronidazole 500mg intravenous four times
a day is equally efficacious. For mild-to-moderate disease
there is no evidence suggesting that it is less effective than
vancomycin . It is not only cheaper than vancomycin
but also achieves effective concentrations in the colon by
both oral and intravenous administration. The response
rates range from 95%  to 50%  over the last 2
decades in all CDI cases. There is a watershed area that
coincides with the emergence of NAP1/B1/027 strain after
Gastroenterology Research and Practice5
Time period of treatment failure rate
Treatment failure rate (%)
Zar et al. 1994-2002
Teasley et al. 1983
Wenisch et al. 1996
Pepin et al. 1991-2002Pepin et al. 2003-2004
Musher et al. 2005
Lagrotteria et al. 2006
Figure 1: Treatment failure rates (%) of metronidazole in C. difficle
infection: The rate of treatment failure with metronidazole has
increased over the last 2 decades. Metronidazole treatment failure
rates (%) however have increased the most after 2000 with the
which there is increase in both initial treatment failure rate
and recurrence rate [2, 24, 70–74] (Figure 1). Even though
C. difficile resistance to metronidazole had been generally
from 7.7% in 1994, 6.3% in 2002 to 12% in 2008 [75–77].
Oral vancomycin is the only FDA approved drug for
CDI. The treatment failure rate of vancomycin is much less
than metronidazole and is unaffected by the emergence of
the new 027 strain (3.4%) [71, 72]. Vancomycin is indicated
for treatment of an initial episode of severe CDI, second C.
pregnant females. In a randomized clinical trial by Zar et al.,
they found that the initial response rate with metronidazole
(250mg four times a day) and vancomycin (125mg four
times a day) was similar in those with mild disease (90% and
98%, resp., P = 0.36). However, in those with severe disease
metronidazole had only a 76% cure rate compared to a 97%
cure rate with vancomycin (P = 0.02) .
The optimal treatment regimen for CDI in IBD patients
is not known. Failure rates of up to 50% have been reported
in IBD patients with metronidazole [6, 79]. Given the worse
outcomes in IBD patients with CDI, some institutions are
practicing a more aggressive approach by using vancomycin
as a first-line drug. By switching the regimen and rapid
decrease in steroid dosing Issa et al. were able to reduce their
institutions colectomy rate within a year [14, 36, 37]. By
following a similar approach, Kariv et al. found that colec-
tomy rates were lower in IBD patients with CDI compared
to IBD patients without CDI. This effect was probably due
to targeted antimicrobial treatment [6, 37]. Certainly for
those patients with a high pretest probability (prior CDI,
recent antibiotic exposure, etc.), empiric treatment with
vancomycin should be considered while awaiting definitive
Studies that looked at other antibiotics like rifampin,
bacitracin, rifaximin, nitazoxanide, and fusidic acid did
not show superior efficacy compared to metronidazole or
vancomycin in treating the first episode of CDI . Fidax-
omicin, a macrocyclic antibiotic, which is approximately
eight times more active in vitro against clinical isolates of
C. difficile than vancomycin was as effective as vancomycin
in rates of clinical cure in a noninferiority trial (88.2% with
fidaxomicin and 85.8% with vancomycin). This trial did
not include patients with IBD but it would be interesting
to evaluate these new drugs in this cohort . A drug,
teicoplanin, which is not available in United States has been
shown to be slightly more efficacious than vancomycin with
RR 1.21 (95% CI 1.00–1.46 P = 0.006), RR 1.82 (95% CI
1.19–2.78 P = 0.0006), and RR 1.43 (95% CI 1.14–1.81
P = 0.002) for initial symptom response, bacteriological
cure, and initial bacterial resolution respectively .
Tigecycline, the first of a new class of broad spectrum
antibiotics, the glycyclines, binds to 30S ribosomal subunit,
inhibiting protein synthesis in a fashion similar to aminogly-
cosides, macrolides, and linezolid . It has been approved
for parenteral treatment of complicated intra-abdominal
and skin infections. The use of tigecycline in treatment of
refractory C. difficile infection has shown promising results
[82, 83]. Tigecycline has higher mean fecal concentration
(mean 5.6mg/L, range 3.0–14.1mg/L) after intravenous
administration of 100mg loading dose followed by 50mg
0mg/L, range 0–10.2mg/L) [81, 84–86]. In critically ill
patients, where there is doubt about adequate drug delivery
of vancomycin through oral or enema route, intravenous
tigecycline provides a reliable source of drug delivery and
efficacy. Even though the results of tigecycline are promising
it should be used with caution in severely ill patients because
of risk of superimposed infection and other complications
8.2. Immunomodulators. CDI can precipitate an IBD flare
olution. In patients who are not already on immunomodula-
IBD. The optimal therapy is unclear and there is little data
to guide us on the most appropriate strategy in this patient
population. A recent retrospective multicenter European
study compared 155 hospitalized IBD patients with CDI
who were treated with antibiotics and immunomodulators
or antibiotics alone. The primary outcome of death or
colectomy within 3 months of admission was reported in
12% of patients treated with antibiotics and immunomod-
ulators as compared to none in the group treated with
antibiotics alone . Immunomodulators included in this
study were corticosteroids (more than or equal to 20mg per
biological agent of any kind . They found that use of
2 or more immunomodulators further increased the risk
of complications (odds ratio 17, 95%; CI 3.2–91) .
Cyclosporine use did not reach statistical significance for the
primary outcome. With respect to infliximab a recent study
looking at the risk of CDI with infliximab in IBD patients
did not show an increased risk . Even though previously
there was compelling evidence that immunomodulators
6Gastroenterology Research and Practice
increase the risk of CDI in IBD patients recent studies have
raised doubts regarding this association.
of the gut. There have been some promising results with the
use of probiotics in preventing antibiotic associated diarrhea
or CDI [88, 89]. The best data exists for Saccharomyces
boulardi which has been shown to be effective in preventing
recurrent CDI . There are studies that evaluate the
primary and secondary preventive roles of probiotics but
none with a focus on IBD patients. As of now there
is insufficient data to recommend use of probiotics with
antibiotics for primary prevention of CDI . There is no
data on use of probiotics alone for treating infection .
8.4. Intravenous (IV) Immunoglobulin. Host immunity is an
important factor in CDI and elevated levels of immunoglob-
ulins against toxin A and B are found in asymptomatic
carriers of C. difficile . IV immunoglobulins have been
tried in about a dozen nonrandomized trials for treatment
of refractory and severe cases [93–96]. There were promising
case report data for severe infection but case control trials
showed equivocal benefit and higher mortality [96–98]. At
this time we recommend use of IV immunoglobulins (IVIG)
only in the context of a prospective trial.
8.5. Surgery. Surgery is indicated in patients with CDI who
have toxic megacolon, perforation hemorrhagic fulminant
infection, and those refractory to medical therapy [37, 99].
Fulminant colitis occurs in 3–8% of C. difficile cases and the
postoperative mortality can be as high as 50% . Patients
with history of IBD, recent surgery, and prior treatment with
IVIGareatincreasedrisk ofdeveloping fulminantcolitis and
and improving outcome [101–103]. Factors contributing to
higher mortality in fulminant colitis, namely, longer hospital
stay (more than 6 days), end organ failure, leukocytosis
(>16,000/μL), vasopressor requirement, and increased lac-
tate, should guide early surgical intervention . Subtotal
colectomy with end ileostomy is the treatment of choice
in CDI . To improve the postoperative survival it is
imperative to have a high clinical suspicion and focus on
early intervention and careful patient selection for colectomy
8.6. Recurrent CDI. In general, C. difficile recurrence can
occur in 15–20% of cases after the first episode and
subsequent rates of recurrence are even higher (33–60%)
[27, 44, 104]. Relapse is defined as infection within 7–14
days of treatment. The persistence of spores in the colon is a
potential source of recurrent infections. There is limited data
regarding risk of CDI recurrence in IBD patients.
IDSA guidelines recommend treatment of the first
episode of recurrent infection with a repeat dose of the first
drug for 10 days. Patients with a second recurrence should
be treated with vancomycin 125mg four times a day for 10–
14 days followed by a tapering regimen (125mg 2 times a
day for 1 week, 125mg once a day for 1 week, then 125mg
every 2-3 days for 2–8 weeks) [70, 105, 106]. Fecal transplant
for floral reconstitution has been tried in some refractory
with positive results and has been effective in IBD patients
. Probiotics (Saccharomyces boulardii) are promising
candidates in combination with other antibiotics to prevent
CDI recurrence in the general population . Monoclonal
antibiotics to treat recurrent infection with some success
in the general population . The optimal treatment of
recurrent disease in IBD patients is unclear and at this time
should be treated like the non-IBD population until further
studies are available.
Environmental disinfection is foremost in the prevention
of CDI. Contamination has been found on 49% of sites in
rooms of C. difficile infected patients and 29% in rooms of
asymptomatic carriers [112, 113]. Alcohol and ammonium-
based cleaning agents act on the vegetative form and are not
effective against spores; in fact, they encourage sporulation.
Chlorine-based disinfectants and high concentration of
vaporized hydrogen peroxide are sporicidal. Nosocomial
transmission of C. difficile can be substantially decreased by
adequate hand washing with soap and water defined as 15–
30 seconds of hand washing and rinsing, followed by drying
using a clean disposable paper towel [78, 113–121]. 1:10
dilution of bleach (concentrated sodium hypochlorite) is an
effective cleaning solution [115, 122, 123].
Prophylaxis of patients on antibiotics or treating asymp-
tomatic carriers is not useful in preventing spread of
infection in the general population [114, 124–127]. Oral
toxoid vaccines that were effective in cows and poultry
were unsuccessful in human studies, likely due to the acidic
environment of the stomach. Parenteral vaccines against
C. difficile have been tried on small number of healthy
volunteers and those with recurrent infection with IgG
response over the threshold but larger studies that show IgA
response are awaited [128–130].
Over the past decade CDI rates have accelerated in healthy
and IBD patient populations. CDI carries special consid-
eration for those with IBD. The risk of CDI is greater in
IBD patients where it is linked to significant morbidity.
CDI also increases the risk of IBD recurrence. CDI leads to
worse outcomes in IBD patients and hence it is important
to test IBD patients presenting with a flare and initiate
therapy early. The subtype of IBD (UC > CD), host factors
like immunosuppression, and extent of colonic involvement
vancomycin is a good alternative to metronidazole in severe
infection and in patients who cannot take metronidazole.
Gastroenterology Research and Practice7
There are no guidelines and limited research data available
to address appropriate therapy in IBD patients and those on
concurrent immunosuppressant therapy who acquire CDI.
Prospective clinical trials are needed. In addition, new ther-
apeutic modalities like immunoglobulins, fecal transplant
are being explored for treatment of severe, refractory, and
recurrent infection. A new drug, fidaxomicin, a macrocyclic
for treatment of CDI [110, 131]. Overall, we recommend
clinicians consider CDI with every flare of symptoms in IBD
patients. Proper identification, treatment, and prevention of
CDI in IBD patients greatly improve outcomes and preserve
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