# 18 - 139 Clostridioides difficile Infection, Including Pseudomembranous Colitis

### 139 Clostridioides difficile Infection, Including Pseudomembranous Colitis

viral enteric pathogens. An effective rotavirus vaccine is available. Vac­
cines against V. cholerae are available and recommended in areas where 
active transmission is ongoing, although the protection they offer is 
incomplete and short lived. A typhoid conjugate vaccine is now recom­
mended by the World Health Organization for use in countries where 
typhoid is endemic. At present, there are no effective commercially 
available vaccines against pathogenic E. coli, Shigella, Campylobacter, 
nontyphoidal Salmonella, norovirus, or intestinal parasites.

Acknowledgment
The authors thank Stephen B. Calderwood, MD, Edward T. Ryan, MD, 
and Richelle C. Charles, MD, for their significant contributions to this 
chapter in the previous editions.
■
■FURTHER READING
Brown AB et al: Travel-related diagnoses among U.S. nonmigrant trav­
elers or migrants presenting to U.S. GeoSentinel Sites – GeoSentinel 
Network, 2012-2021. MMWR Surveill Summ 72:1, 2023.
Global Burden of Disease Cause of Death Collaborators: Global, 
regional, and national age-sex-specific mortality for 282 causes of death 
in 195 countries and territories, 1980-2017: A systematic analysis for the 
Global Burden of Disease Study 2017. Lancet 392:1736, 2018.
Goldenberg JZ et al: Probiotics for the prevention of pediatric antibioticassociated diarrhea. Cochrane Database Syst Rev 12:CD004827, 2015.
Guttman JA, Finlay BB: Subcellular alterations that lead to diarrhea 
during bacterial pathogenesis. Trends Microbiol 16:535, 2008.
Hyesuk S et al: Vaccines against gastroenteritis, current progress and 
challenges. Gut Microbes 11:1486, 2020.
Levine MM et al: Diarrhoeal disease and subsequent risk of death 
in infants and children residing in low-income and middle-income 
countries: Analysis of the GEMS case-controlled study and 12-month 
GEMS-1A follow-on study. Lancet Glob Health 8:e202, 2020.
Local Burden of Disease Diarrhoea Collaborators: Mapping geo­
PART 5
Infectious Diseases
graphical inequalities in childhood diarrhoeal morbidity and mortal­
ity in low-income and middle-income countries, 2000-17: Analysis 
for the Global Burden of Disease Study 2017. Lancet 395:1779, 2020.
Rodgers AP et al: Impact of enteric bacterial infections at and beyond 
the epithelial barrier. Nat Rev Microbiol 21:260, 2023.
Shane AL et al: Infectious Diseases Society of America. Clinical practice 
guidelines for the diagnosis and management of infectious diarrhea. 
Clin Infect Dis 65:e45, 2017.
Teh R et al: Review of the role of gastrointestinal multiplex polymerase 
chain reaction in the management of diarrheal illness. J Gastroenterol 
Hepatol 36:3286, 2021.
Tsolis RM, Baumler AJ: Gastrointestinal host-pathogen interaction 
in the age of microbiome research. Curr Opin Microbiol 53:78, 2020.
Dale N. Gerding, Stuart Johnson

Clostridioides difficile 

Infection, Including 
Pseudomembranous Colitis
■
■DEFINITION
Clostridioides difficile infection (CDI) is a unique colonic disease that 
is acquired most commonly in association with antimicrobial use and 
the consequent disruption of the normal colonic microbiota. The most 
commonly diagnosed diarrheal illness acquired in the hospital, CDI 
results from the ingestion of spores of C. difficile that vegetate, multi­
ply, and secrete toxins, causing diarrhea and, in the most severe cases, 
pseudomembranous colitis (PMC).

■
■ETIOLOGY AND EPIDEMIOLOGY
C. difficile is an obligately anaerobic, gram-positive, spore-forming 
bacillus whose spores are found widely in nature, particularly in the 
environment of hospitals and chronic-care facilities. CDI occurs fre­
quently in hospitals and nursing homes (or shortly after discharge from 
these facilities) where the level of antimicrobial use is high and the 
environment is contaminated by C. difficile spores.
Clindamycin, ampicillin, and cephalosporins were the first antibiot­
ics associated with CDI. The second- and third-generation cephalospo­
rins, particularly cefotaxime, ceftriaxone, cefuroxime, and ceftazidime, 
are agents frequently responsible for this condition, and the fluoroqui­
nolones (ciprofloxacin, levofloxacin, and moxifloxacin) are the most 
recent drug class to be implicated in hospital outbreaks. Penicillin/

β-lactamase-inhibitor combinations such as ticarcillin/clavulanate and 
piperacillin/tazobactam pose significantly less risk. However, all anti­
biotics, including vancomycin (the agent most commonly used to treat 
CDI), have been found to carry a risk of subsequent CDI. A minority 
of cases, especially in the community, are reported in patients without 
documentation of prior antibiotic exposure.
C. difficile is acquired exogenously—most often in the hospital or 
nursing home, but also in the outpatient setting—and is carried in the 
stool of both symptomatic and asymptomatic patients. The rate of fecal 
colonization increases in proportion to length of hospital stay and is 
often ≥20% among adult patients hospitalized for >2 weeks; in contrast, 
the rate is 1–3% among community residents. CDI is the most com­
mon health care–associated infection in the United States, with an esti­
mated 462,100 cases in 2017. Between 2011 and 2017, the total burden 
of CDI in the United States decreased by 24%, which was due primarily 
to decreases in health care–associated CDI. The estimated burden of 
community-associated CDI was unchanged, but it now approximates 
the health care–associated rate in the United States.
Asymptomatic fecal carriage of C. difficile in healthy neonates is 
very common, with repeated colonization by multiple strains in infants 
<1–2 years of age, but associated disease in these infants is extremely 
rare if it occurs at all. Spores of C. difficile are found on environmental 
surfaces (where the organism can persist for months) and on the hands 
of hospital personnel who fail to practice good hand hygiene. Hospital 
epidemics of CDI have been attributed to a single C. difficile strain 
and to multiple different strains, introduced by patients on admission, 
that are present simultaneously. Other identified 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, and no firm data have impli­
cated these agents in patients who are not already receiving antibiotics.
■
■PATHOLOGY AND PATHOGENESIS
Spores of toxigenic C. difficile are ingested, survive gastric acidity, ger­
minate in the small bowel, and, in the presence of a disrupted micro­
biota, colonize the lower intestinal tract, where they elaborate two 
large toxins: toxin A (an enterotoxin) and toxin B (a cytotoxin). These 
toxins initiate processes resulting in the disruption of epithelial-cell 
barrier function, diarrhea, and pseudomembrane formation. Toxin A 
is a potent neutrophil chemoattractant, and both toxins glucosylate the 
GTP-binding proteins of the Rho subfamily that regulate the actin cell 
cytoskeleton. Data from studies using molecular disruption of toxin 
genes in isogenic mutants suggest that toxin B may be the more impor­
tant virulence factor, which is consistent with the well-documented 
occurrence of clinical disease caused by toxin A–negative strains but 
not by toxin B–negative strains. Disruption of the cytoskeleton results 
in loss of cell shape, adherence, and tight junctions, with consequent 
fluid leakage. A third toxin, binary toxin CDT, was previously found in 
only ~6% of strains but is present in all isolates of the widely recognized 
epidemic NAP1/BI/027 strain (see “Global Considerations,” below); 
this toxin is related to C. perfringens iota toxin. Its role in the pathogen­
esis of CDI has not yet been defined.
The pseudomembranes of PMC are confined to the colonic mucosa 
and initially appear as 1- to 2-mm whitish-yellow plaques. The inter­
vening mucosa appears unremarkable, but, as the disease progresses,

FIGURE 139-1  Autopsy specimen showing confluent pseudomembranes covering 
the cecum of a patient with pseudomembranous colitis. Note the sparing of the 
terminal ileum (arrow).
the pseudomembranes coalesce to form larger plaques and become 
confluent over the entire colon wall (Fig. 139-1). The whole colon 
is usually involved, but 10% of patients have rectal sparing. Viewed 
microscopically, the pseudomembranes have a mucosal attachment 
point and contain necrotic leukocytes, fibrin, mucus, and cellular 
debris. The epithelium is eroded and necrotic in focal areas, with neu­
trophil infiltration of the mucosa.
Patients colonized with C. difficile were initially thought to be at 
high risk for CDI. However, four prospective studies have shown that 
colonized patients who have not previously had CDI actually have a 
decreased risk of CDI, possibly because many of these patients are 
colonized by nontoxigenic strains. At least three events are proposed 
as essential for the development of CDI (Fig. 139-2). Exposure to anti­
microbial agents is the first event and establishes susceptibility to CDI, 
most likely through disruption of the normal gastrointestinal micro­
biota. The second event is exposure to toxigenic C. difficile. Given that 
the majority of patients do not develop CDI after the first two events, 
a third event is clearly essential for its occurrence. Candidate third 
C. difficile
exposure
C. difficile
exposure
Antimicrobial(s)
Healthcare Exposure
(Increased chance of 
receiving an antibiotic and 
Increased chance of being 
exposed to spores of C. difficile)
FIGURE 139-2  Pathogenesis model for Clostridioides difficile infection (CDI). At least three events are integral to C. difficile pathogenesis. Exposure to antibiotics 
establishes susceptibility to C. difficile infection. If susceptible, the patient may ingest nontoxigenic (nonpathogenic) or toxigenic strains of C. difficile as a second event. 
Acquisition of toxigenic C. difficile may be followed by asymptomatic colonization or CDI, depending on one or more additional factors, including the strain of C. difficile and 
an inadequate host anamnestic antibody response to C. difficile toxins.

events include exposure to a C. difficile strain of particular virulence, 
exposure to antimicrobial agents especially likely to cause CDI, and 
an inadequate host immune response. The host anamnestic immune 
response as has been shown for serum IgG antibody response to toxin 
A of C. difficile is likely one factor in the third event that determines 
which patients develop diarrhea and which patients remain asymp­
tomatic. The majority of humans probably first develop antibody to C. 
difficile toxins when colonized asymptomatically during the first year 
of life or after CDI in childhood. Infants are thought not to develop 
symptomatic CDI because they lack suitable mucosal toxin receptors 
that develop later in life. In adulthood, there is evidence that serum 
antibodies to both toxin A and B protect against recurrent CDI. Two 
large clinical trials in which intravenous monoclonal antibodies to 
toxin A and toxin B were used together and as single agents in addi­
tion to standard antibiotic therapy showed that rates of recurrent CDI 
were significantly lower with the combination of antibodies and with 
the toxin B antibody alone than with placebo plus standard therapy. 
Antibody to toxin A alone was ineffective.

■
■GLOBAL CONSIDERATIONS
Rates and severity of CDI in the United States, Canada, and Europe 
increased markedly in the early 2000s. Rates in U.S. hospitals tripled 
between 2000 and 2005. Hospitals in Montreal, Quebec, reported 
rates in 2005 that were four times higher than the 1997 baseline, with 
directly attributable mortality of 6.9% (increased from 1.5%). An epi­
demic strain, variously known as toxinotype III, REA type BI, PCR 
ribotype 027, and pulsed-field type NAP1 (collectively designated 
NAP1/BI/027), likely accounted for much of the increase in incidence. 
Two clones of NAP1/BI/027 originated in the United States and 
Canada and spread to the United Kingdom, Europe, and Asia. This epi­
demic strain was characterized by (1) an ability to produce 16–23 times 
as much toxin A and toxin B as control strains in vitro, (2) the presence 
of binary toxin CDT, and (3) high-level resistance to all fluoroquino­
lones. National control policies instituted in England in 2006 resulted 
in a marked decline in CDI cases, and restriction of fluoroquinolones, 
in particular, was correlated with near elimination of fluoroquinoloneresistant strains of C. difficile (i.e., NAP1/BI/027) there by 2013. This 
epidemic strain has likewise decreased in the United States, with 
data from the Centers for Disease Control and Prevention showing a 
decrease among health care–associated isolates from 31% to 15% (and 
from 19% to 6% in community-associated isolates) between 2011 and 
2017. New strains have been and will probably continue to be impli­
cated in outbreaks, including a strain commonly found in food animals 
that also carries binary toxin and has been associated with high mortal­
ity rates in human infections (toxinotype V, ribotype 078). Currently, 
the most frequently isolated community-associated strain in the United 
States is ribotype 106 (REA group DH), which was previously found to 
be epidemic in the United Kingdom.
CHAPTER 139
Clostridioides difficile Infection, Including Pseudomembranous Colitis 
Asymptomatic 
C. difficile
colonization
CDI
Acquisition of a
toxigenic strain of 
C. difficile and
presence of additional
factor(s) result in CDI.

■
■CLINICAL MANIFESTATIONS
Diarrhea is the most common manifestation caused by C. difficile. 
Stools are almost never grossly bloody and range from soft and 
unformed to watery or mucoid in consistency, with a characteristic 
odor. Clinical and laboratory findings include fever in 28% of cases, 
abdominal pain in 22%, and leukocytosis in 50%. When adynamic 
ileus (which is seen on x-ray in ~20% of cases) results in cessation of 
stool passage, the diagnosis of CDI is frequently overlooked. A clue 
to the presence of unsuspected CDI in these patients is unexplained 
leukocytosis, with ≥15,000 white blood cells (WBCs)/μL. Such patients 
are at high risk for complications of CDI, particularly toxic megacolon 
and sepsis.

C. difficile diarrhea recurs after treatment in ~15–30% of cases and 
remains one of the most challenging treatment dilemmas. Recurrences 
may represent either relapses due to the same strain or reinfections 
with a new strain. Susceptibility to recurrence of clinical CDI is likely 
a result of continued disruption of the normal fecal microbiota caused 
by the antibiotic used to treat CDI.
■
■DIAGNOSIS
The diagnosis of CDI is based on a combination of clinical criteria: (1) 
diarrhea (≥3 unformed stools per 24 h for ≥2 days) with no other rec­
ognized 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 (NAAT; e.g., polymerase chain reaction [PCR]) or by culture, 
or visualization of pseudomembranes in the colon. PMC is a more 
advanced form of CDI and is visualized at endoscopy in only ~50% of 
patients with diarrhea who have a positive stool culture and toxin assay 
for C. difficile (Table 139-1). Endoscopy is a rapid diagnostic tool in 
seriously ill patients with suspected PMC and an acute abdomen, but a 
negative result in this examination does not rule out CDI.
PART 5
Infectious Diseases
Despite the array of tests available for C. difficile and its toxins 
(Table 139-1), no single test has high sensitivity, high specificity, 
and rapid turnaround. Most laboratory tests for toxins, including 
enzyme immunoassays (EIAs), lack sensitivity. NAATs (including 
PCR) are widely used diagnostically and are both rapid and sensitive; 
however, concern has been raised that PCR may detect colonization 
with toxigenic C. difficile in patients who have diarrhea for a reason 
other than CDI. Confirmation of the presence of toxin in the stool 
in addition to NAAT or glutamate dehydrogenase (GDH) positivity 
is recommended in the European CDI guidelines for diagnosis of 
CDI, and inclusion of a stool toxin test is recommended in the U.S. 
guidelines when there are no prior criteria for stool submission. Test 
algorithms that include NAAT followed by toxin EIA for NAAT+ 
results, and GDH plus toxin EIA arbitrated by NAAT when the two 
initial test results do not agree, have become widely used; however, 
when results of individual algorithm tests are discrepant (NAAT+ or 
GDH+/toxin EIA–), most patients are nonetheless treated for CDI. 
TABLE 139-1  Relative Sensitivity and Specificity of Diagnostic Tests for Clostridioides difficile Infection (CDI) 
TYPE OF TEST
RELATIVE SENSITIVITYa
RELATIVE SPECIFICITYa
COMMENT
Stool culture for C. difficile
++++
+++
Most sensitive test; specificity of ++++ if the C. difficile isolate tests 
positive for toxin; turnaround time too slow for practical use
Cell culture cytotoxin test on stool
+++
++++
With clinical data, is diagnostic of CDI; highly specific but not as 
sensitive as stool culture; slow turnaround time
Enzyme immunoassay for toxins A and 
B in stool
++ to +++
+++
With clinical data, is diagnostic of CDI; rapid results, but not as sensitive 
as stool culture or cell culture cytotoxin test
Enzyme immunoassay for C. difficile 
common antigen in stool
+++ to ++++
+++
Detects glutamate dehydrogenase found in toxigenic and nontoxigenic 
strains of C. difficile and other stool organisms; more sensitive and less 
specific than enzyme immunoassay for toxins; requires confirmation 
with a toxin test; rapid results
Nucleic acid amplification tests for 
C. difficile toxin A or B gene in stool
++++
+++
Detects toxigenic C. difficile in stool; widely used in United States for 
clinical testing; more sensitive than enzyme immunoassay toxin testing; 
marked increase in CDI diagnoses when implemented
Colonoscopy or sigmoidoscopy
+
++++
Highly specific if pseudomembranes are seen; insensitive compared 
with other tests
aAccording to both clinical and test-based criteria.
Note: ++++, >90%; +++, 71–90%; ++, 51–70%; +, ~50%.

Empirical treatment is appropriate if stool testing is delayed. Testing 
of asymptomatic patients is not recommended except for epidemio­
logic study purposes. In particular, so-called tests of cure following 
treatment are not recommended because >50% of patients continue 
to harbor the organism and its toxin after diarrhea has ceased and test 
results are not predictive of recurrence of CDI. The results of such 
tests should not be used to restrict placement of patients in long-term 
care or nursing home facilities.
TREATMENT
Clostridioides difficile Infection 
PRIMARY CDI
When possible, discontinuation of any ongoing antimicrobial 
administration is recommended as the first step in treatment of 
CDI. Earlier studies indicated that 15–23% of patients respond to 
this simple measure. However, with the advent of the NAP1/BI/027 
epidemic strain and the associated rapid clinical deterioration of 
some patients, prompt initiation of specific CDI treatment has 
become the standard. General treatment guidelines include hydra­
tion and the avoidance of antiperistaltic agents and opiates, which 
may mask symptoms and possibly worsen disease. Nevertheless, 
antiperistaltic agents have been used safely with vancomycin or 
metronidazole treatment for mild to moderate CDI.
Oral administration of fidaxomicin was suggested as firstline treatment for CDI in the 2021 Infectious Diseases Society 
of America (IDSA) and Society for Healthcare Epidemiology of 
America (SHEA) focused update guidelines on management of 
CDI in adults. However, because of resource availability issues, 
oral vancomycin remains an acceptable alternative. Oral metro­
nidazole is recommended only for mild or moderate CDI when 
fidaxomicin or vancomycin is not available. IV vancomycin is 
ineffective for CDI. Fidaxomicin is available only for oral admin­
istration. Two large clinical trials comparing vancomycin and 
fidaxomicin indicated comparable clinical resolution of diar­
rhea in ~90% of patients, and the rate of recurrent CDI was 
significantly lower with fidaxomicin. The largest randomized 
controlled trial of vancomycin versus metronidazole showed that 
the vancomycin cure rate was superior to the metronidazole cure 
rate (81% vs 73%; p = .034) for all patients with CDI, regardless 
of severity. Although the mean time to resolution of diarrhea is 
2–4 days, the response to metronidazole may be much slower. 
Treatment should not be deemed a failure until a drug has been 
given for at least 6 days. On the basis of data for shorter courses 
of vancomycin and the results of four large clinical trials, it is 
recommended that vancomycin or fidaxomicin be given for at 
least 10 days. Metronidazole was never approved for CDI by the

TABLE 139-2  Recommendations for the Treatment of Clostridioides difficile Infection (CDI)
CLINICAL SETTING
TREATMENT(S)
COMMENTS
Initial episode, mild to 
moderate
Fidaxomicin (200 mg bid × 10 d) or alternatively
Oral vancomycin (125 mg qid × 10 d)
Initial episode, severe
Oral vancomycin (125 mg qid × 10 d) or alternatively
Fidaxomicin (200 mg bid × 10 d)
Initial episode, fulminant
Vancomycin (500 mg PO or via nasogastric tube) plus 
metronidazole (500 mg IV q8h) plus consider
Rectal instillation of vancomycin (500 mg in 100 mL of normal 
saline as a retention enema q6–8h)
First recurrence
Fidaxomicin (200 mg bid × 10 d) or
Oral vancomycin (125 mg qid × 10 d) or
Oral vancomycin followed by a taper-and-pulse regimena
Multiple recurrences
Oral vancomycin treatment followed by a taper-and-pulse 
regimen or
Fidaxomicin (200 mg bid × 10 d or 200 mg bid × 5 d followed by 
every other day × 20 d) or
Vancomycin (125 mg qid × 10 d), then stop vancomycin and 
start rifaximin (400 mg bid × 2 weeks) or
Fecal microbiota replacement therapy (FMRT)
Patients at high risk of 
recurrent CDI who are 
receiving vancomycin, 
fidaxomicin, or 
metronidazole
Bezlotoxumab 10 mg/kg given IV
Bezlotoxumab is adjuvant therapy (in addition to and during antibiotic 
treatment) for patients at high risk for recurrent CDI. Risk factors include 
age >65 years, immunocompromised host, severe CDI on presentation, 
and prior episode of CDI in the past 6 months.
aA typical taper-and-pulse vancomycin regimen following a 10-day treatment course includes: 125 mg bid × 1 week, then daily × 1 week, then q2–3d for 2–8 weeks.
U.S. Food and Drug Administration (FDA), and its use for CDI 
treatment declined markedly after publication of the 2017 IDSA/
SHEA CDI guidelines. It is important to initiate treatment with 
oral vancomycin or fidaxomicin for patients who appear seriously 
ill, particularly if they have a high WBC count (>15,000/μL) or 
creatinine level (≥1.5 mg/dL) (Table 139-2). Small randomized 
trials of nitazoxanide, bacitracin, rifaximin, and fusidic acid for 
treatment of CDI have been conducted. These drugs have not 
been extensively studied, shown to be superior, or approved by the 
FDA for CDI, but they provide potential alternatives to vancomy­
cin and fidaxomicin. 
RECURRENT CDI
Overall, ~15–30% of successfully treated patients experience 
recurrences of CDI following treatment. CDI recurrence is sig­
nificantly lower in patients treated with fidaxomicin than in those 
treated with vancomycin. Vancomycin and metronidazole have 
comparable recurrence rates, and metronidazole is not recom­
mended for treatment of recurrent CDI. Patients who have a 
first recurrence of CDI have an even higher rate of second recur­
rence. Fidaxomicin is superior to vancomycin in reducing further 
recurrences in patients who have had one CDI recurrence (Table 
139-2). Recurrent disease, once thought to be relatively mild, has 
now been documented to pose a significant (11%) risk of seri­
ous complications (shock, megacolon, perforation, colectomy, or 
death within 30 days). There is no standard treatment for multiple 
recurrences, but the use of vancomycin in a tapering and pulsed 
dosing regimen every other day for 2–8 weeks has been used 
for years as a practical approach to treating these patients, and 
recent data suggest it is still effective. Other recommended treat­
ment options for patients with multiple CDI recurrences include 
fidaxomicin in standard or extended/pulsed dosing regimens, 
vancomycin followed by rifaximin, or fecal microbiota transplan­
tation (FMT) via nasoduodenal tube, colonoscope, enema, or oral 
capsules (Table 139-2). FMT has been widely used over the past 
decade, and the availability of stool banks and oral capsule formu­
lations made this approach more practical. Recently, the FDA has 
approved two microbiota replacement therapies and discontinued 
enforcement discretion for centralized donor stool banks. A fecal 

Oral metronidazole is less effective than the other options and may 
necessitate a longer treatment course for response. Metronidazole 
(500 mg tid × 10–14 d) is recommended only if vancomycin or fidaxomicin 
is not readily accessible and for mild to moderate disease only.
Indicators of severe disease may include leukocytosis (≥15,000 white 
blood cells/μL) and a creatinine level ≥1.5 mg/dL.
Fulminant CDI is defined as severe CDI with the addition of hypotension, 
shock, ileus, or toxic megacolon. The duration of treatment may need to 
be >2 weeks and is dictated by response.
Treatment for the initial episode may be considered when choosing 
treatment for the first recurrence.
It is recommended that FMRT by fecal microbiota (Rebyota, live-jslm) 
given by enema or fecal microbiota spores (Vowst, live-brpk) given orally 
be considered only after appropriate antibiotic treatment for recurrent 
CDI.
CHAPTER 139
microbiota suspension (Rebyota, live-jslm) and a suspension of 
live fecal microbiota spores for oral delivery (Vowst, live-brpk) are 
now approved for patients with recurrent CDI to prevent further 
recurrence. Both of these products are adjunctive treatments that 
are indicated for patients who have completed antibiotic treat­
ment for CDI.
Clostridioides difficile Infection, Including Pseudomembranous Colitis 
In addition to antibacterial therapies, another adjunctive treat­
ment is now available for patients who are receiving standard-ofcare antibacterial agents and who are at high risk for recurrent CDI 
(rCDI). Bezlotoxumab, a monoclonal antibody directed against 
C. difficile toxin B, has been shown to reduce the risk of rCDI by 
an absolute rate of ~10% when administered to patients currently 
receiving vancomycin, fidaxomicin, or metronidazole. Risk factors 
for rCDI in the clinical trials included age >65 years, immunocom­
promise, severe CDI on presentation, and prior episode of CDI in 
the past 6 months. 
SEVERE COMPLICATED OR FULMINANT CDI
Fulminant (rapidly progressive and severe) CDI presents the most 
difficult treatment challenge. Patients with fulminant disease often 
do not have diarrhea, and their illness mimics an acute surgical 
abdomen. Sepsis (hypotension, fever, tachycardia, leukocytosis) 
may result from fulminant CDI. An acute abdomen (with or with­
out toxic megacolon) may include signs of obstruction, ileus, colonwall thickening and ascites on abdominal CT, and peripheral-blood 
leukocytosis (≥20,000 WBCs/μL). With or without diarrhea, the 
differential diagnosis of an acute abdomen, sepsis, or toxic megaco­
lon should include CDI if the patient has received antibiotics in the 
past 2 months. Cautious sigmoidoscopy or colonoscopy to visualize 
PMC and an abdominal CT examination are the best diagnostic 
tests in patients without diarrhea.
Medical management of fulminant CDI is suboptimal because 
of the difficulty of delivering oral fidaxomicin, metronidazole, or 
vancomycin to the colon in the presence of ileus (Table 139-2). 
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, as has IV tigecycline in 
small-scale uncontrolled studies. Surgical colectomy may be life­
saving if there is no response to medical management. If possible,