Syllabus

CHAPTER 11

Gastrointestinal infections of
the small intestine and colon
Christina M. Surawicz, MD and Amy Barto, MD

Educational objectives
After completing this chapter, the learner should be able to:
1. Identify organisms that affect the small intestine and cause generally noninvasive diarrhea
2. Identify organisms that affect the ileocolonic area and often cause invasive diarrheas
3. Review the role of diagnostic tests for evaluation of acute diarrhea
4. Review the rationale for empiric antibiotic treatment in some cases of infectious diarrhea
5. Identify infectious agents that can cause chronic diarrhea

Introduction
Worldwide, infectious agents are the most common cause of diarrhea and are a major contribution to
morbidity and mortality in developing countries, especially in epidemics, which often affect children. Current
food distribution practices have resulted in the rapid, efficient and wide dissemination of infectious agents
in developed countries. Leafy green vegetables are the most common cause of food borne illness, accounting
for 1 in 4 cases in the US. Other examples of food borne illness include Shiga toxin Escherichia coli (STEC)
0157:H7 infection due to contaminated ground beef and unpasteurized apple juice, Cyclospora infection
associated with imported raspberries, and Listeria monocytogenes with lunch meats and cantaloupes.
Travelers to developing countries can acquire a variety of infectious agents that cause acute (and occasionally
chronic) diarrhea. Pathogens that cause diarrhea can generally be assigned to 1 of 2 groups: small intestinal
pathogens, which are typically noninvasive, and ileocolonic pathogens, which are often invasive.
Generally, infectious gastroenteritis is self-limited, but mortality can occur. Currently, Clostridioides
difficile is the most common cause of death due to GI infections, followed by norovirus. Listeria is less
common but is the most deadly, with a fatality rate of 17 percent.

Pathophysiology
Diarrhea is defined as 3 or more loose or unformed stools daily. An objective definition of diarrhea is
more than 200 to 300 g of stool per 24 hours. The mechanisms of diarrhea include decreased absorption,
increased secretion, increased luminal osmolality, and changes in gut motility. Bacterial enteropathogens
cause diarrhea by 1 or more of several mechanisms:

• Enterotoxin production. Adhesive enterotoxigenic bacteria adhere to intact microvilli and se-
crete enterotoxins that stimulate secretion and/or impair absorption. Examples of these are Vibrio
cholerae and enterotoxigenic E coli (ETEC).

365
366 Digestive Diseases Self-Education Program®
• Cytotoxin production. These toxins cause
cell injury and inflammation. An example is C
difficile.
• Preformed toxin. Some bacteria produce
toxins in contaminated food; when ingested,
the toxins cause acute symptoms, usually nau-
sea and vomiting. Examples of these are Staph-
ylococcus aureus and Bacillus cereus.
• Enteroadherence. Organisms adhere to the
intestinal mucosa, where they attach and efface
absorptive cells. Examples of these are entero-
pathogenic E coli (EPEC) and enterohemor-
rhagic E coli (EHEC)
• Mucosal invasion with inflammation
and/or ulceration. These organisms pen-
etrate the mucosa, spread, and cause mucosal
damage with erosions and ulcers. Examples
are Shigella, enteroinvasive E coli, and Cam-
pylobacter jejuni.
• Penetration of the mucosa and prolif-
eration in the submucosa. Examples are
Salmonella and Yersinia enterocolitica.
Many organisms cause disease by more than one
mechanism. In addition to the above, inflammation
induces release of intestinal secretagogues, includ-
ing arachidonic acid metabolites, kinins, and vaso-
active substances. The net result of these processes
is secretion of water and electrolytes. Toxin produc-
tion mediates intestinal secretion directly; this can
be amplified by the autonomic nervous system with
increased transit. Mucosal mast cells may play a role
in the recruitment of white blood cells.
Clinical presentation
There are general differences in the presentation
of small bowel versus colonic infection (Table 11.1),
but overlap is common. Diarrhea due to small in-
testinal disease is typically high volume, watery,
and often associated with diffuse mid-abdominal
pain and cramps. Malabsorption can occur and
dehydration is frequent. Diarrhea due to colonic
pathogens is generally smaller in volume, but de-
hydration can still occur. Stools may be bloody
when invasive pathogens are involved. Lower ab-
dominal pain is frequent, and tenesmus may oc-
cur, especially when there is rectal involvement.
Because there is significant overlap in clinical pre-
sentation, diagnostic tests are needed to make a
specific diagnosis.
Infectious agents that cause diarrhea can be
classified either as (1) small intestinal pathogens,
which are often noninvasive, or (2) ileocolonic
pathogens, which are more likely to be invasive
(Table 11.2). The pathogens most frequently found
in the small intestine are viruses but can also in-
clude enterotoxigenic E coli, Vibrio cholerae, and
Salmonella species. Most small intestinal para-
sites are typically non or minimally invasive: Giar-
dia lamblia, Cystoisospora belli, Cyclospora, and
Cryptosporidia. The most common colonic patho-
gens are bacteria, such as Campylobacter, Shi-
gella, Salmonella and Shiga toxin E coli. Parasites
include Amoeba and Trichuris. Some organisms
affect both small bowel and colon (Salmonella,
Listeria, Strongyloides).
Infections can be associated with symptoms
outside the gastrointestinal (GI) tract. Examples
are hemolytic uremic syndrome due to Shigella or
Shiga toxin–E coli (STEC), reactive arthritis asso-
ciated with Yersinia or other bacterial pathogens,
and Guillain-Barré syndrome following Campylo-
bacter infection.
Table 11.1
Characteristics of infectious diarrhea
Small intestinal Colonic
Large volume
stools
Small volume
stools
Can be
Watery
bloody
Diffuse abdominal Lower abdominal
pain/cramps pain
Malabsorption Tenesmus
Dehydration Dehydration
 Chapter 11 — GI infections of the small intestine and colon 367

Specific infections – Table 11.2

Source of infectious diarrhea
Small intestinal pathogens
Small intestine Ileocolonic
Viruses
Viral gastroenteritis is the most common cause of Viruses
Viruses
n Rotavirus
acute diarrhea worldwide, in both children and n Cytomegalovirus
n Norovirus
n Herpes simplex
adults, accounting for 75 percent of all infectious n Adenovirus (enteric)
virus type II
diarrhea.1 These viruses include rotavirus, norovi- n Astrovirus
rus, enteric adenovirus, astrovirus, and torovirus.
Bacteria Bacteria
These are self-limited illnesses that typically cause n Campylobacter species
n Vibrio cholera
acute diarrhea with associated vomiting. n Salmonella n Salmonella species
Rotavirus and, to a lesser extent, enteric ad- n Toxigenic E coli n Shigella species
(ETEC, EPEC, EAEC) n Eshericia coli 0157:H7 (EHEC)
enovirus are the most common cause of acute di-
n Aeromonas hydrophila n Yersinia
arrhea in children. Rotavirus is the main cause of n Clostridium difficile
n Listeria monocytogenes
diarrhea in children less than 2 years of age and is n Tuberculosis n Noncholera Vibrio
highly contagious, commonly spreading in day care n Aeromonas hydrophila
n Plesiomonas shigelloides
centers and among family members. Adenovirus
n EIEC
types 40 and 41 have been found in stools from 8.6 n Listeria monocytogenes
percent of young children with acute gastroenteri- n Tuberculosis
tis. Viruses are spread by fecal-oral contamination,
aerosolized vomitus, contaminated food and fomi- Parasites Parasites
tes. Examples include norovirus acquired from n Giardia lamblia n Amoeba
leafy green vegetables and from raw oysters from n Cryptosporidia n Cryptosporidia
n Isospora belli
contaminated freshwater estuaries. n Cyclospora cayetanensis
Norovirus can cause diarrhea in all age groups
and sickens 5.5 million people in the US yearly.
ETEC, enterotoxigenic E coli; EPEC, enteropathogenic E coli; EAEC,
Food handlers are responsible for 50 to 80 percent enteroaggregative E coli; EHEC, enterohemorrhagic E coli; EIEC,
of cases. There have been well publicized epidemics enteroinvasive E coli
of norovirus on cruise ships and in long term care
facilities. can be up to 14 days. Severe dehydration in chil-
Norovirus is the most common cause of acute dren can lead to death. Individuals can remain con-
gastroenteritis worldwide. It is very contagious, tagious for up to 3 weeks, Alcohol hand gels may not
because the number of virions to cause infection is adequately kill viruses nor prevent transmission in
small, it is hard to remove from the environment, hospitals, although studies suggest that their use
and because 15 to 35 percent of infections are as- does reduce transmission. Careful hand washing
ymptomatic. Moreover, it can cause vomiting with- with soap and water is therefore important to pre-
out diarrhea, so it is likely that the rates of infection vent transmission.
are under reported. After ETEC, it is the most com- Rotavirus can be detected in stool samples by
mon cause of traveler’s diarrhea. There is no long- electron microscopy or PCR among other methods.
lasting immunity, so reinfection can occur. However, diagnostic tests for viral gastroenteritis
Rotavirus infections are most common in chil- are not readily available and are usually unneces-
dren; symptoms are mild to severe diarrhea with sary, as these illnesses are typically self-limited.
vomiting and fever in severe cases. Symptoms usu- Treatment primarily involves maintaining oral re-
ally begin 24 to 72 hours after ingestion of the or- hydration. Vaccines for rotavirus are now available
ganisms. The illness typically lasts 3 to 7 days but for use in infants and children, but not adults. Vac-
368 Digestive Diseases Self-Education Program®
cines have significantly reduced the rate of hospi-
talization for rotavirus infection in children in the
US.2 Of note, rotavirus vaccine is a live vaccine and
should be avoided in the first 6 months of life for
infants of mothers with inflammatory bowel dis-
ease on anti-TNF medications.
Bacteria
Escherichia coli
There are several strains of E coli that may cause
diarrhea. Those that affect the small intestine in-
clude enterotoxigenic (ETEC), entero-pathogenic
(EPEC), enteroaggregative (EAEC), and diffusely
adherent (DAEC). These all cause disease by en-
terotoxin production or adhesion to the brush bor-
der. The symptoms are self-limited watery diarrhea
with vomiting or fever. The typical incubation pe-
riod ranges from several hours to two days and in-
fection usually lasts 3 days or less. Nausea, cramps,
and fever are less common.
ETEC, EAEC, and DAEC can all cause traveler’s
diarrhea (TD). EAEC is associated with diarrhea in
children (both in developing countries and in the
US). It can be chronic in children who are malnour-
ished or immunocompromised and is recognized
as an emerging food-borne pathogen. EPEC, which
is uncommon, causes acute and chronic diarrhea in
children and sporadic epidemic infantile diarrhea
(weanling diarrhea), a severe problem in malnour-
ished children in developing countries.
Treatment is fluid replacement. In severe cas-
es, ETEC can be treated with antibiotics (quino-
lones, rifaximin or azithromycin) and anti-motility
agents, but the latter should not be used in cases
of severe dysentery. In Southeast Asia, there is in-
creasing resistance of ETEC to quinolones, limiting
their usefulness.
Vibrio cholera
There are two biotypes of V cholera: 01, the classic
strain and El Tor, both of which can cause epidem-
ics. These are usually non-invasive organisms.
V cholerae 01 causes epidemic cholera, but is
rare in travelers. The pathogen colonizes the up-
per small intestine but is noninvasive so it does not
cause bacteremia. Diarrhea is due to stimulation
of cAMP-mediated chloride secretion, inhibition
of sodium absorption, and production of platele-
tactivating factor, with possible resulting altera-
tion in prostaglandin synthesis. Treatment is oral
rehydration solutions and antibiotics (single-dose
doxycycline or ciprofloxacin). Two oral cholera
vaccines are available. Although they do not pro-
vide 100 percent protection, they can be used for
travelers to high risk areas.
Listeria
Listeria infection is not a common food borne in-
fection, but is associated with high-morbidity and
mortality. The organism resists salts, nitrates,
acid, and freezing and can multiply in refrigerated
products. Multiple epidemics of Listeria monocy-
togenes gastroenteritis have been linked to con-
taminated chocolate milk, lunch meats, and un-
pasteurized cheeses, contaminated cantaloupes,
seafood and ice cream. There are two forms of
Listeria: (1) noninvasive, which typically causes a
febrile illness with nausea, vomiting, and diarrhea,
and (2) invasive, with similar symptoms, but is as-
sociated with septicemia and meningoencephalitis.
The illness is associated with increased morbidity
and mortality in immunocompromised patients,
especially those with hematologic malignancies, as
well as pregnant women and neonates. Pregnant
women have a 100-fold increased risk of listeriosis
and a 20-fold increase in miscarriage and still birth.
In pregnant women with invasive illness, the fetus
can be infected via the placenta and this may lead
to spontaneous abortion, stillbirth, or sepsis in the
neonate. Infections are most common in the third
trimester of pregnancy. There may be fever, muscle
aches, and headache with meningeal involvement.
Diagnosis is often made by blood culture. Vaginal
cultures are not helpful as women may be asymp-
tomatic carriers. Routine stool cultures are often
negative and false positives can occur as people can
be asymptomatic carriers.
Parasites—protozoa
Parasites can cause a wide variety of symptoms
(Table 11.3). Protozoal infections are the most com-
mon small-intestinal parasites. Cryptosporidium,
 Chapter 11 — GI infections of the small intestine and colon 369

Table 11.3 has not been established. Symptoms include diar-

Association of parasites with specific clinical syndromes rhea, nausea, vomiting, abdominal cramps, bloat-
ing and gas. There may be fat malabsorption.
Malabsorption Chronic infection can occur in immunocom-
  Coccidiosis petent individuals, as well as those with immu-
  Giardia
  Strongyloides nocompromising conditions including hypogam-
  Capillariasis maglobulinemia, IgA deficiency, common variable
  Cryptosporidia immunodeficiency and HIV. Some people are as-
  Isospora belli
ymptomatic cyst excreters. The diagnosis typically
Diarrhea with blood rested on detection of cysts in the stool (3 stools
  Amebiasis
  Schistosomiasis
over 6 days, since excretion is intermittent); one
  Trichuriasis stool exam has a yield of 50 to 70 percent. How-
Occult blood in stools ever, now most laboratories use a more sensitive
  Hookworm EIA to detect Giardia antigen in the stool, as it will
  Strongyloides pick up 30 percent more cases than stool micros-
Chronic tropical diarrhea copy. Newer multiplex panels using PCR to detect
  Parasites multiple GI pathogens are becoming more widely
    Ameba
   Post amebic dysentery
available, and may be used as well to detect Giardia
    Giardia lamblia and other pathogens. Duodenal aspiration for tro-
    Coccidiosis phozoites lacks sensitivity and is not routinely per-
      Cryptosporidia formed. Duodenal biopsies can be helpful. Villous
      Isospora belli
   Tropical sprue
blunting and increased intraepithelial lymphocytes
mimicking celiac disease can occur and the Giardia
Cyclospora cayetanensis, Giardia duodenales (G. trophozoites can be seen by microscopy with routine
lamblia and G. intestinalis) and Cystoisospora belli H&E staining. Treatment with metronidazole, ni-
(formerly Isospora belli), and microsporidia (now re- tazoxanide, or tinidazole is typically curative, but 10
classified as fungi). Giardia lamblia and Cryptospo- to 20 percent of patients relapse and require repeat
ridium parvum are the most common in the US. All treatment. Post-infectious irritable bowel syndrome
except Giardia invade epithelial cells. (IBS) is commonly seen after Giardia infection.

Giardia
Giardia is a protozoal flagellate and is a common
waterborne cause of diarrhea worldwide. Giardia
cysts are chlorine-resistant and outbreaks have
occurred in areas with chlorinated but unfiltered
water. Cysts can remain viable for months, even in
cold water. Cysts also are resistant to gastric acid.
Transmission can occur by fecal-oral transmission,
as may occur with epidemics in day care centers,
drinking contaminated water (typically associated
with camping), or with anal sex. The incubation pe-
riod is 1 to 2 weeks. Cysts form in the lumen and are
excreted in stools. As few as 10 to 25 cysts can cause
disease when they transform into the pathogenic
trophozoites which attach to the duodenal and je-
junal mucosa, though the mechanism of diarrhea
Cryptosporidiosis
There are 26 species that infect humans; the most
common Cryptosporidium species are C hominis
and C parvum. Fecal contamination of water leads
to ingestion of oocysts, but person-to-person and
animal-to-person transmission also occurs. The
sporozoites most commonly infect the small in-
testine, where they attach to enterocytes between
their microvilli. In immunocompromised individu-
als, organisms can be seen in colonic, pancreatic,
and biliary mucosa.
Cryptosporidium has caused many epidemics
in the US via contaminated water. The organism is
chlorine-resistant and can even persist despite the
use of state-of-the-art water-treatment facilities.
Outbreaks have been reported in day care centers,
370 Digestive Diseases Self-Education Program®
among livestock/veterinary workers, and in wa-
terparks. Asymptomatic carriage can contribute to
epidemics.
Clinically, diarrhea is profuse and watery and
lasts for up to 1 month. In most people, the illness is
self-limited, but in immunocompromised persons
it can be chronic and even fatal. In those with HIV
infection and a low CD4 cell count, antiretroviral
therapy can be effective, as the infection may clear
when the CD4 cell count rises above 200/µL. Diag-
nosis is made by stool examination of 3 stools, using
acid-fast stains or immunofluorescent monoclonal
antibodie,s as well as antigen-detection assays and
polymerase chain reaction (PCR). Nitazoxanide is
approved by the US Food and Drug Administration
(FDA) for use in treatment of Cryptosporidium
parvum (and G lamblia) infection.
Cyclospora cayetanensis
Cyclospora cayetanensis is a protozoan that causes
prolonged watery diarrhea. Initial reported cases
from travelers to Nepal and an outbreak among hos-
pital workers in Chicago were likely due to contami-
nated water. Highly publicized outbreaks associated
with raspberries from Guatemala were reported
in 1996 and 1997. Infection rates in these epidem-
ics were very high (82 percent). Now, outbreaks
are more associated with leafy green vegetables
like basil. Cyclospora causes prolonged diarrhea
(4-6 weeks) with nausea, vomiting, myalgia, and
cramps, usually without fever. Diagnosis is made
by stool exam but may be missed with traditional
ova and parasite exams, thus special stains of stool
may be needed. Treatment with trimethoprim-sul-
famethoxazole shortens the duration of the illness.
Cystoisospora belli
Cystoisospora belli (formerly Isospora belli) is rec-
ognized as a pathogen in both immunocompetent
and immunocompromised individuals. It is present
worldwide, but commonly acquired in tropical and
sub-tropical areas and only infects humans. The
most common symptom is diarrhea that can last for
2 to 3 weeks, and carriage for 3 weeks longer. Those
who are immunocompromised can have chronic diar-
rhea. Transmission is by the fecal-oral route. Diag-
nosis is made by stool exam or small bowel biopsy.
Cystoisospora is unique among the protozoa, as it
causes peripheral eosinophilia and Charcot-Leyden
stool crystals. Treatment is with trimethoprim sul-
famethoxazole.
Parasites-helminth
There are 3 categories of helminths: nematodes
(roundworms), cestodes (tapeworms), and trema-
todes (flukes, eg, Clonorchis and Schistosoma).
Ascaris
The nematode Ascaris is a common parasite
worldwide that infects humans with an estimated
1.5 billion persons infected. Worms can live in the
small bowel for up to two years and grow to 35 cm
in length. Infection is often asymptomatic. Heavy
infestation can cause pneumonia, small bowel,
appendiceal, or biliary obstruction and pancre-
atitis. Treatment is with mebendazole or alben-
dazole, although pyrantel pamoate is used during
pregnancy.
Hookworm
Hookworm infection with Ancylostoma duodenale
and Necator americanus are also common. The
larvae penetrate the skin (and can cause “ground
itch”) with subsequent migration into blood ves-
sels. The larvae are carried in the blood to the lung
and from the alveoli, they move into the bronchi
and then the pharynx and are eventually swal-
lowed. Symptoms are diarrhea, vague abdominal
pain, and nausea. Eosinophilia is common and
because the worms consume up to 0.5 cc of blood
daily, iron deficiency anemia is also usually seen.
Empiric treatment with albendazole should be con-
sidered if clinical suspicion is high.
Strongyloides
Strongyloides stercoralis is found in tropical and
semitropical areas, including Southeast Asia, ru-
ral southern US, and northern Italy. The organism
is free living in the soil, but its presence is unre-
lated to sanitation. It is estimated that 100 million
people worldwide are infected. A notable high-risk
population are persons with HTLV-1 infection.
 Chapter 11 — GI infections of the small intestine and colon
Infection starts when the filariform larvae in soil
burrow into the skin. This is associated with a ser-
piginous urticarial rash (larva currens) on the but-
tocks, perianal area, and feet. The larvae then access
the circulation and spread to the lungs where they
can cause cough. Once coughed up, they are then
swallowed, after which they migrate into the small
intestine. Unlike most parasites, Strongyloides can
complete its life cycle entirely within the human host
and the rhabditiform larvae can develop into infec-
tive filariform larvae within the small bowel lumen.
Typical GI symptoms are nausea, vomiting, an-
orexia, and vague abdominal pain, with infection
of the small bowel and rarely, the colon. The larvae
can be seen on small bowel biopsies. Eosinophilia is
common (present in 75 percent). Colitis can occur
and is often right-sided.
Diagnosis of Strongyloides can be difficult.
Stool detection of larvae may only be 30 percent.
Serology (IgG antibody) is the best diagnostic test
(84–100 percent sensitive) but may not differenti-
ate carriers from those with acute disease and can
take weeks to perform. The combination of stool
and serology will give a diagnostic yield of 89 per-
cent. Treatment is ivermectin.
Because Strongyloides can complete its life-
cycle entirely within the human host, immuno-
suppressed patients can develop a hyperinfection
syndrome when a high worm burden triggers a
systemic inflammatory response. Polymicrobial
bacteremia can occur as the result of superinfec-
tion, as well as pneumonitis and brain involve-
ment. Hyperinfection syndrome has a high fatality
rate. Because delay in diagnosis and treatment of
disseminated strongyloidiasis among immuno-
suppressed patients can have dire consequences,
pre-transplant screening of high-risk individuals is
recommended in most transplant centers. Serology
(IgG ELISA antibody testing) is recommended for
anyone from endemic areas, or who has GI symp-
toms or eosinophilia before transplant. Serology is
better than stool screening, which has sensitivity of
15 to 30 percent for a single stool but up to 100 per-
cent if 7 stools are examined. Treatment should in-
clude ivermectin and empiric antibiotics. Immune
suppressive therapy should be stopped, if possible.
371
Tapeworms
The 4 major cestodes, or tapeworms, are Taenia
saginata (from beef), Taenia solium (from pork),
Diphyllobothrium latum (from freshwater fish),
and Hymenolepis nana (the dwarf tape-worm).
Taenia can be as long as 10–12 meters, and Diphyl-
lobothrium can be up to 12 meters long.
H nana, the most common tapeworm in the
US, is acquired from ingesting fecally contaminat-
ed food. The worms are typically 30 to 40 mm long
and 1 mm wide.
Humans with tapeworms are often asymp-
tomatic. Nonspecific GI symptoms include nau-
sea, anorexia, and epigastric pain. D. latum is
acquired from eating raw freshwater fish and can
cause chronic diarrhea and megaloblastic anemia
from vitamin B12 deficiency due to competition
for vitamin B12. Eosinophilia is common. Diagno-
sis is made by finding eggs or proglottids in stools.
Treatment for all tapeworms is praziquantel.
Specific infections—
ileocolonic pathogens
Bacteria
Campylobacter
Campylobacter species are a major cause of diar-
rheal illness in the world and are the most com-
mon enteric bacterial infection in the US. C jejuni
is most common, followed by C coli. Poultry is the
leading source of infection, although organisms are
also transmitted by the fecal-oral route, or by con-
taminated milk, eggs, or water. Initial symptoms
develop 1 to 7 days after ingestion and include nau-
sea, anorexia, cramping, and watery or bloody di-
arrhea lasting a week or (rarely) longer. The illness
can mimic appendicitis (as can Yersinia). Colitis
is common as are extraintestinal manifestations,
most notably post-infectious arthritis and Guillain-
Barré syndrome (GBS). Campylobacter is thought
to be the cause of 40 percent of GBS cases and
roughly 1 in 1,000 patients with C jejuni infection
will develop GBS. It is not known whether treat-
ment of C jejuni alters the likelihood of developing
372 Digestive Diseases Self-Education Program®
GBS so mild-to-moderate illness does not gener-
ally require antibiotic treatment. Therapy is recom-
mended for severe disease or for symptoms that last
longer than a week. The recommended antibiotic is
azithromycin with ciprofloxacin as an alternative.
Ciprofloxacin-resistant strains are increasing world-
wide, especially in Southeast Asia, and can be associ-
ated with a more severe and prolonged course.
Salmonella
There are more than 2,200 serotypes of Salmonella,
including S enteritidis, S heidelberg, S newport, and
S typhimurium.16 They are the second most common
bacterial pathogens that affect humans. Salmonella
species can cause two very different clinical syn-
dromes—nontyphoidal (gastroenteritis and colitis)
and typhoidal (typhoid fever). The spectrum of illness
ranges from asymptomatic carriage to fatal illness.
Nontyphoidal salmonella
gastro-enteritis
Enterocolitis from infection with S typhimurium,
S newport, S enteritidis is a common cause of bac-
terial diarrhea in the US, with an estimated 1 to 2
million cases yearly. The most common manifesta-
tion is an acute illness with small intestinal involve-
ment, but the colon can also be affected. Many con-
taminated foods have transmitted Salmonella but
the most common vehicles are poultry, egg yolks,
fresh produce, ground beef, and milk. Pet turtles
and snakes can be carriers of the organism and
thus a source of infection. The incubation period is
12 to 72 hours.
Salmonella infection is often a self-limited ill-
ness. The typical symptoms are diarrhea, abdomi-
nal cramps and fever. Dysentery is uncommon.
While usually self-limited, systemic infection with
bacteremia can occur, which accounts for remote
infections in such places as artificial joints or heart
valves, occurs in 2 to 14 percent of cases. This is
more common in immune compromised patients
as well as those with sickle cell anemia, schistoso-
miasis, and hypochlorhydria.
Diagnosis is made by stool culture and occa-
sionally by blood culture. PCR tests are available
for rapid diagnosis but often still require confirma-
tory testing of positive results.
Antibiotics are not usually recommended for
nontyphoidal Salmonella infection. Antibiotics re-
duce the numbers of bacteria, but may not reduce
the duration of symptoms and so are generally re-
served for those with severe symptoms, in infants
or the elderly, in immunocompromised patients or
others with severe underlying illness, in those with
prosthetic joints or heart valves, or if systemic dis-
ease is suspected. When treatment is indicated, such
as with severe disease or underlying illness, antimi-
crobial treatment can be ceftriaxone, ciprofloxacin,
TMP-SX or amoxicillin depending on susceptibility.
Strains with dual quinolone and ceftriaxone resis-
tance have been reported. These strains may cause
more invasive illness and bacteremia. A carrier state
is diagnosed if stools remain positive for over a year.
Quinolones may be effective to treat the carrier state.
Typhoid fever
Typhoid fever is caused by S typhi and is rare in
the US but common in developing countries. Some
non-typhi strains can cause an illness that mim-
ics typhoid (S paratyphi and S choleraesuis). The
organism invades the intestinal mucosa and then
spreads through the blood; thus, diarrhea is un-
common, with constipation occurring frequently
early in the illness. Transmission of non-typhi
strains occurs from consuming contaminated food
(especially poultry, eggs, and dairy products) or wa-
ter. S typhi is only a human pathogen and infection
is typically acquired by travel to settings in which
sanitation is poor or contact with a known typhoid
case or carrier. The incidence is highest in infants
(2-4 months of age) and the elderly. The diagnosis
is made by blood culture early in the course of the
illness, and potentially by stool culture later. There
are 4 classically described stages to the disease:
· Week 1: nonspecific symptoms, including
· fever and chills
· Week 2: right lower quadrant pain, diarrhea
and rose spots
· Week 3: complications such as colon ulcers
with bleeding or perforation
· Week 4: resolution
 Chapter 11 — GI infections of the small intestine and colon
The current treatment of choice is ceftriaxone or cip-
rofloxacin. However, multidrug-resistant strains
can be resistant to fluoroquinolones. Alternatives
include erythromycin or TMP-SX, and ampicillin.
Chloramphenicol no is longer recommended.
Shigella
Shigella is common worldwide. It causes colitis and
has two pathogenic mechanisms: direct invasion of
the colonic epithelium and production of an entero-
toxin. Most human infection is due to 1 of 4 species:
S dysenteriae, S flexneri, S boydii, and S sonnei.
Pandemics are usually associated with S dysente-
riae. In the US, infection with S sonnei is most com-
mon, followed by S flexneri.
Humans are the only natural host for these bac-
teria, which are usually spread by fecal-oral contact
or, less commonly, by contaminated food or water.
Infections are most common in children (age 1 to 4
years), men who have sex with men, travelers, and
people in institutions. Risk factors include exposure
to sewage, and those who live with poor sanitary
conditions. The organism is virulent, and ingestion
of less than 100 organisms can cause disease. The
usual incubation period is 1 to 4 days.
Clinically, the illness begins with a two-day
prodrome of fever, cramps, and secretory diarrhea.
Over the next few days, the bacteria localize to the
colon, causing invasion, ulcers, and inflammation.
With dysentery, left colon and rectal involvement
are prominent. The initial symptoms of nausea,
cramps, and watery diarrhea subside, followed by
bloody mucoid diarrhea and tenesmus, fever, and
systemic toxicity. The major cause of death is dehy-
dration, but other potentially lethal complications
of shigellosis include intestinal perforation, toxic
megacolon, dehydration and sepsis. Extraintes-
tinal complications such as seizures (usually with
fever), encephalopathy, hemolytic uremic syn-
drome, pneumonia, and reactive inflammatory
arthritis can occur. These complications may be
more likely in young malnourished children. Treat-
ment of Shigella infection is always recommended.
Chronic symptoms are rare.
Current WHO guidelines for treatment are for
quinolones first line, with beta lactams and ceph-
373
alosporins as second line.5 Quinolone resistance is
increasing and thus azithromycin is appropriate as
a second line therapy in regions where this is com-
mon. Systemic administration of second-and third-
generation cephalosporins has also been used for
systemic illness. It is not known whether therapy
can prevent complications of shigellosis.
E. coli
Enteroinvasive E coli (EIEC), which causes an ill-
ness that resembles Shigella sonnei infection, but is
generally mild and can be treated with a quinolone.
Shiga toxin E coli (STEC)
Shiga toxin E coli (STEC), formerly known as
Enterohemorrhagic E coli (EHEC), includes the
0157:H7 strain and can cause hemorrhagic colitis
and distal ileitis. One hundred serotypes cause hu-
man disease. The 0157 strains and non-0157 strains
often cause epidemics; sporadic cases also occur.
Non-0157 STEC infections may account for up to
50 percent of STEC infections. The peak season for
infection is the summer.
E coli 0157:H7 was first recognized as a cause
of hemorrhagic colitis in 1982. The organism is usu-
ally acquired from unpasteurized milk or under-
cooked ground beef, although there are other ve-
hicles, including unpasteurized apple juice, basil,
pesto, sprouts, venison, and petting zoos. The most
common route of acquisition of STEC is food and
water that is contaminated by cattle manure (even
though the cattle are usually asymptomatic). Per-
son to person contact can cause secondary infec-
tion, and even contaminated water ingested while
swimming can cause infection. Some waterborne
epidemics have occurred, as well as an epidemic
at a county fair where bacteria were dispersed by
an airborne route. The organism itself is not inva-
sive, but it produces a Shiga-like toxin. The typi-
cal presentation is nausea, vomiting, low-grade or
absent fever, followed within 2 to 3 days by severe
abdominal pain and diarrhea, which often becomes
bloody within 2 to 3 days of the onset of watery di-
arrhea. Symptoms usually resolve within a week
unless there are complications. Colonic involve-
ment with the 0157:H7 strain is often localized to
374 Digestive Diseases Self-Education Program®
the right side; thus, in elderly patients, the clini-
cal presentation might mimic ischemic colitis,
and in a pediatric population, the initial diagnosis
might be intussusception or inflammatory bowel
disease. Severe complications are hemolytic ure-
mic syndrome (HUS), a microangiopathic hemo-
lytic anemia with thrombocytopenia, renal failure,
and thrombocytopenic purpura. HUS occurs in
10 percent of children age younger than 11, most
commonly in those younger than 5, and in 2 to 8
percent of adults. The risk of HUS in children is 5
to 15 percent, with an overall mortality up to 25
percent. Rates of long-term renal disease is high
with HUS. Up to half of children will require renal
dialysis. Predictors of HUS include short incuba-
tion period, high white blood cell count, high C-
reactive protein, and low serum albumin. Sequelae
may include permanent kidney damage, seizures
due to CNS involvement with vasculitis, and death.
STEC and Shigella are the most common causes
of HUS in the US. The Shiga like toxins I and II
are absorbed, causing endothelial damage to blood
vessels, platelet aggregation, thrombi, and micro-
vascular ischemia.
Diagnosis depends on detecting the organism
in the stools; it is recommended for labs to test
for Shiga toxin to distinguish E coli 0157:H7 from
other STEC strains.
Several publications indicate that both anti-
biotic treatment and antimotility agents are asso-
ciated with an increased risk of HUS in children,
probably because antibiotics increase release of
toxins by the organism; thus, antibiotics and anti-
diarrheals are contraindicated in STEC infection
and supportive therapy with fluids is best.
The importance of non-0157:H7 strain is high-
lighted by the epidemic of STEC 0104:H4 that oc-
curred in Germany in 2011 due to contaminated
sprouts. The outbreak caused 3,816 documented
infections, 54 deaths, with a very high rate of HUS
with 845 (22 percent) confirmed cases. More-
over, unlike STEC 0157:H7, most (88 percent) of
the HUS cases were in adults. This organism was
identified as an enteroaggregative Shiga toxin pro-
ducing E coli 0104:H4 and was traced to fenugreek
seeds imported from Egypt.
Enteroaggregative E. coli
Enteroaggregative E coli are emerging as endemic in
Central Asia and spreading to Asia and Europe, and
can cause traveler’s diarrhea and childhood diarrhea.
It is likely that humans are the only reservoir.
Clostridioides (Clostridium) difficile
C difficile is the most common nosocomial infec-
tion of the GI tract. This Gram-positive anaerobe
causes disease by production of 2 toxins. Toxin A
is an enterotoxin while toxin B is a cytotoxin. Most
strains produce both toxin A and toxin B or toxin
B alone, no cases have been reported with Toxin
A alone. Antibiotics are the most common cause
of C difficile infection (CDI) and any antibiotic can
be implicated. Common risk factors include older
age, comorbid conditions, immunosuppression,
inflammatory bowel disease, recent hospitalization
or residence in a long term care facility. Epidem-
ics have been documented in hospital settings, and
long-term care facilities. However, sporadic com-
munity cases in otherwise healthy individuals are
on the rise, possibly up to one-third of cases, some
without preceding antibiotic exposure. This may
be a result of an epidemic strain, Nap1 BI/027, that
emerged in the year 2000 and some develop CDI
without prior antibiotic use. This strain possesses
a partial gene deletion that causes increased pro-
duction of toxins A and B in vitro and may explain
its increased virulence. Clindamycin and quinolone
resistance are a characteristic of this strain. Wide-
spread quinolone use may explain some epidemics
that are notable for increased morbidity and mor-
tality, as well as increases in metronidazole treat-
ment failure rates. There are other hypervirulent
strains. There is increasing evidence that proton
pump inhibitor therapy predisposes to CDI through
disruption of the intestinal microbiome.
CDI, formerly called C difficile–associated di-
arrhea, should be suspected in anyone who devel-
ops unexplained diarrhea (defined as greater than
or equal to 3 unformed stools within 24 hours)
during or soon after antibiotic therapy. Diarrhea
can even occur up to 8 weeks after the end of a
course of antibiotics. Keep in mind that antibiotics
 Chapter 11 — GI infections of the small intestine and colon
themselves commonly cause diarrheal side effects,
and thus diagnostic testing for C difficile should
be undertaken prior to empiric treatment. Proper
contact and isolation precautions should be used
pending results. Given the increase in CDI in oth-
erwise healthy individuals with no risk factors or
antibiotic exposure, one should test for C difficile
in cases of new, unexplained diarrhea as well as se-
vere or prolonged diarrhea. Diagnosis rests on de-
tection of C difficile in the stools, either by toxin or
by the organism, and only diarrheal stools should
be tested. In the past, EIA tests for toxins A and B
were widely used, but while very specific, they are
not sensitive enough to be stand-alone tests. A posi-
tive result needs to be confirmed. The EIA for the
glutamase dehydrogenase (GDH antigen) is very
specific but not sensitive, so it is also sometimes
used as a screen; when negative no further testing is
done, but a positive result requires a confirmatory
test. Most laboratories use nucleic acid amplifica-
tion tests (NAAT), including PCR for the C difficile
toxin B gene.
When there are clear testing criteria, (ie, new
unexplained diarrhea, with 3 or more diarrheal
stools in a 24hour period and no obvious cause
such as laxatives in a hospitalized patient), an NAAT
test like PCR for toxin B is a reasonable diagnostic
test, and is the most commonly used stand-alone
test. It has excellent sensitivity and specificity. If
the test is negative, it should not be repeated as
yield is low. The major limitation of PCR is that it
cannot distinguish between active infection and
carrier state because it does not test for active
toxin and thus has the potential for overtreatment
of carriers whose diarrhea may be due to another
cause. Note that 5 to 15 percent of healthy adults
may be carriers. This is higher in patients recently
hospitalized or in long-term care facilities (LTCFs).
This has led some experts to recommend a multi
-step testing algorithm to detect organisms and to
detect toxins. One strategy is an EIA for the GDH
antigen as an initial screen for patients at increased
risk for CDI. This should be part of a multistep
protocol with subsequent confirmatory EIA for
the toxin with or without PCR. For patients likely
to have CDI based on symptoms, PCR testing CDI,
375
testing using PCR together with EIA toxin allows
discernment between carrier state and active infec-
tion. Retesting should not be done within 7 days, in
asymptomatic patients or to test for cure. The tox-
in can remain positive for up to 2 to 8 weeks after
eradication, and the PCR testing even longer due to
persistent shedding. Although PCR has excellent
diagnostic sensitivity and specificity, it is not 100
percent accurate. Thus, in an ill patient in whom di-
agnostic tests do not confirm the clinical suspicion,
empiric therapy should be strongly considered.
Toxigenic culture is usually reserved for evalu-
ation of epidemics. White blood cells may be pres-
ent in the stools, but are not a reliable indicator of
colitis; they were absent in 70 percent of toxin-pos-
itive stools in one study.
C difficile causes a range of symptoms from
asymptomatic carriage to mild diarrhea to severe
disease with pseudomembranous colitis that can
be fatal. Treatment is based on severity of disease,
which has been traditionally classified into 1 of 3
categories: mild to moderate (also called non-se-
vere), severe and severe—complicated (also called
fulminant). The 2017 Infectious Disease Society of
America (IDSA) published updated guidelines in
early 2018 for the treatment of initial and recur-
rent CDI with a notable change in the treatment of
initial episodes. For those with mild to moderate
disease, the recommendation is vancomycin or fi-
daxomicin due to lower efficacy of metronidazole in
more severe cases. Fidaxomicin use may be limited
by its high cost, however. In all cases, the inciting
antibiotic should be discontinued if possible as this
can influence recurrence.
In patients with mild to moderate CDI as de-
fined by diarrhea without signs of more severe dis-
ease (ie, normal white blood cell count, creatinine,
albumin) the initial recommended treatment is
vancomycin 125 mg orally four times daily for 10
days, or fidaxomicin 200 mg orally twice daily for
10 days. If these agents are not available or contra-
indicated, oral metronidazole can be given 500 mg
orally three times daily for 10 days. Criteria for se-
vere CDI include a white blood cell (WBC) count of
greater than or equal to 15,000/µL, hypoalbumin-
emia (less than 3 g/dL) and abdominal distension
376 Digestive Diseases Self-Education Program®
and tenderness and can include a creatinine greater
than 1.5 mg/dL.
Severe CDI is treated similarly with vancomy-
cin 125 mg orally four times daily for 10 days, or
fidaxomicin 200 mg orally twice daily for 10 days.
Fulminant (also termed severe-complicated) CDI
is defined as severe disease with hypotension or
shock, ileus, or megacolon. Additional criteria from
other societies include fever, WBC greater than
35,000/µL or less than 2000/µL, lactate greater
than 2.2 mmol/L or multiorgan failure, especially
lungs or kidneys. In these patients, oral vancomy-
cin should be started at 500 mg every 6 hours and
supplemented by intravenous metronidazole, 500
mg every 8 hours. Vancomycin enemas can also be
added (500 mg of intravenous
[IV] vancomycin in 100 mL normal saline every
6 hours), especially if there is an ileus. Fecal micro-
biota transplant (FMT) can be used for fulminant
CDI, but data on its efficacy are limited to case series
and retrospective studies. When used, a consolida-
tion FMT is often required within one week.
The use of antidiarrheals and antimotility
agents such as narcotics is contraindicated in these
critically ill patients. Serial clinical evaluation is
important to look for signs that urgent surgery may
be needed. A surgical series from Quebec evaluated
patients with severe CDI and identified clinical pre-
dictors of 30-day mortality: elevated lactate (great-
er than 5 mmol/L), elevated white blood cell counts
(greater than 20,000/µL), being on pressors, and
being age 75 years or older. These patients should
be considered for early colectomy.8 Surgery, when
indicated, has traditionally involved a total colecto-
my with ileostomy, but more recently a loop ileos-
tomy with vancomycin irrigation of the colon is an
appealing alternative as it preserves the colon. In
one study, mortality with the loop ileostomy was 19
percent compared with historical controls who had
subtotal colectomy in whom mortality was 50 per-
cent.9 In many patients, the ileostomy can be taken
down later. Mortality from fulminant toxic colitis
or perforation ranges from 2 to 8percent.
There has been a marked increased incidence
of CDI in patients with IBD, up to 2 or 3 times
higher than in the previous decade and they have
higher morbidity and mortality than patients with
IBD alone or CDI alone. Risk factors are immuno-
modulator therapy and colonic disease (rates are
higher for patients with ulcerative colitis than with
Crohn’s disease) and urgent colectomy is more
common in those with CDI.23 Pseudomembranes
may be absent on colonoscopy. There may be no
prior antibiotic use. These patients should be
given vancomycin as their first-line drug even if
mild disease, and experts recommend holding any
increase in immune suppressive therapy for a few
days as the CDI is treated. 10 Evaluation is compli-
cated since symptoms of both diseases are similar.
Consultation with an IBD expert is recommended.
Most patients with CDI respond to treatment with
resolution of diarrhea, but 20 percent of patients
will have recurrence; these patients are even more
likely to have further recurrences (40–65 percent).
The pathophysiology is likely related to persis-
tently abnormal colon microbiota and an impaired
immune response. Risk factors include older age,
intercurrent antibiotics, renal disease, and prior
recurrences. This is becoming an increasingly chal-
lenging clinical problem. The initial therapeutic ap-
proach to recurrent CDI is to repeat the same or an
alternate antibiotic. For a first recurrence, the IDSA
guidelines recommend oral vancomycin 125 mg
four times daily for 10 days if metronidazole was
used initially, or, a vancomycin taper if vancomy-
cin was used initially. A simple vancomycin taper
is vancomycin 125 mg four times daily orally for 10
days followed by one dose of vancomycin 125
mg every 3 days for 10 more doses. Fidaxomicin
200 mg twice daily for 10 days can also be used if
vancomycin was used initially. If recurrences con-
tinue, FMT may be the best next option, with cure
rates of 90 percent overall.
FMT is the process of instilling stool from
healthy donors into the colon of patients with CDI,
either by enema, colonoscopy, nasogastric, or na-
soenteric route. Multiple meta-analyses showed ef-
ficacy of FMT ranging from 85 to 90 percent with
few complications. There are now 5 published ran-
domized controlled trials showing efficacy of FMT
for recurrent CDI. The first gave stool via nasoduo-
denal infusion, and was stopped early since the
 Chapter 11 — GI infections of the small intestine and colon
treatment group had so many fewer recurrences
compared to the control groups who had vanco-
mycin alone or vancomycin with gut lavage.11 Most
recently, capsules of frozen stool given orally were
as effective as frozen stool given via colonoscope.12
Guidelines from multiple societies including
the American College of Gastroenterology (2013),
European Society of Clinical Microbiology and In-
fectious Diseases (ESCMID; 2014), European Con-
sensus (2017), and IDSA (2018) recommend FMT
for multiply recurrent CDI. The FDA currently ex-
ercises enforcement discretion for the use of FMT
to treat patients with recurrent or refractory CDI.
All other indications should be part of a clinical
trial. Patient evaluation is important to make sure
the CDI has truly recurred and not another cause of
diarrhea, such as post infectious IBS, IBD or micro-
scopic colitis. Donor screening is necessary to make
sure there are no GI illnesses, systemic diseases, in-
fections, metabolic syndrome among others.13 Both
blood and stool must be screened for pathogens.
Frozen stool from stool banks using pre-screened
donors is currently being used as a widespread
alternative to patient identified donors. The most
common complications are transient fevers, con-
stipation, and bloating. A few infections have been
documented such as norovirus, presumably from
the donor stool. In 2019, an immunocompromised
patient in a clinical trial for FMT died after infec-
tion with extended-spectrum beta lactamase E coli,
traced back to an asymptomatic donor who was not
prescreened for this bacterium. This prompted the
FDA to require screening of all donors for multi-
drug resistant organisms (MDROs).27 In patients
with IBD treated with FMT for RCDI, some have
had flares of inflammatory bowel disease. FMT is
effective for treatment of RCDI in IBD patients, but
its use for treatment of IBD should be limited to
clinical trials. Long-term safety data are limited to
retrospective series; in one series, 3 of 77 patients
developed a new autoimmune condition over subse-
quent years.14 FMT appears safe in immunocompro-
mised patients, with efficacy of 89 percent in one
retrospective series and no infections related to the
FMT.15 A registry has been funded by the NIH and
AGA that will give long term follow up data.
377
Yersinia
Yersinia enterocolitica and Yersinia pseudotu-
berculosis are pathogens that can cause acute or
chronic colitis. Infection commonly results from
ingestion of contaminated milk products or pork
(especially chitterlings [hog intestine]). Y entero-
colitica causes mesenteric adenitis, terminal il-
eitis and colitis, usually 4 to 7 days after ingestion.
Symptoms can last up to 3 weeks. Patients with
iron overload conditions like hemochromatosis are
more likely to develop bacteremia. When the ill-
ness presents with right lower quadrant pain due
to acute terminal ileitis with mesenteric adenitis,
it can be misdiagnosed as acute appendicitis or
Crohn’s disease. Reactive arthritis may begin 2 to
3 weeks later, and is associated with HLAB27 posi-
tivity. The colonoscopic features include aphthoid
ulcers, which occur more commonly in the right
side of the colon; terminal ileoscopy can show ede-
ma, ulcers, and round or oval elevations of the mu-
cosa. The organism can be cultured from stool, but
a special cold-enrichment technique is necessary,
and results may not be available for a week or lon-
ger. Cultures of lymph nodes, blood, or peritoneal
fluid may also be positive, but it may take weeks for
the organism to grow. In a typical clinical setting,
serology with elevated antibody titers may be use-
ful to make the diagnosis.
In most cases treatment is not necessary, but it
may be prudent to treat severe enteritis, mesenter-
ic adenitis, and those with erythema nodosum and
arthritis. Recommended treatment is TMP-SMX;
cefotaxime or ciprofloxacin are alternatives.
Aeromonas
Aeromonas species (A hydrophila, A caviae, A
veronii biovar sobria) can cause a self-limited wa-
tery diarrhea, often in children.5 Infection is often
associated with ingestion of contaminated food
or water. Aeromonas causes enteritis and rarely
dysentery. An acute colitis that mimics ischemic
colitis, ulcerative colitis or Crohn’s disease occurs
rarely, but it is not clear if these infections actually
cause chronic colitis or if they trigger the onset of
IBD. A study from Spain found that when Aeromo-
378 Digestive Diseases Self-Education Program®
nas caused traveler’s diarrhea, half the patients
went on to have chronic diarrhea.16 The role of
therapy is unclear, but effective antibiotics include
quinolones, and azithromycin. One should treat if
symptoms are severe.
Plesiomonas
Plesiomonas shigelloides is an invasive pathogen
that can cause acute diarrhea and rarely dysentery.
Contaminated food and water are the most com-
mon sources. Persistent diarrhea has been report-
ed in some cases. The role of therapy is not clear,
but probably indicated for severe cases.
Noncholera vibrios
Noncholera Vibrio such as V parahaemolyticus
and V vulnificus cause diarrhea by invading the co-
lonic mucosa. The illness is usually associated with
eating raw or under cooked shellfish. Noncholera
Vibrio species cause a self-limited illness with nau-
sea, vomiting, and diarrhea. V vulnificus may man-
ifest with ecchymotic, bullous skin lesions. Patients
with chronic liver disease are at increased risk and
should never eat raw or undercooked shellfish, as
they can develop a fatal infection. Other risk factors
are diabetes, iron overload conditions, immuno-
suppression, and achlorhydria. Treatment is usu-
ally not indicated for noninvasive disease, but, dual
therapy is indicated with ceftriaxone plus doxycy-
cline for invasive disease.
Tuberculosis
Intestinal tuberculosis (TB) is uncommon in the
US but can be seen in immigrants from endemic
areas. It most frequently involves the ileocecal area
and can closely mimic Crohn’s disease. Only half of
patients will have concomitant pulmonary involve-
ment. Diarrhea is uncommon but abdominal pain
is present in 80 to 90 percent of patients. Skin tests
(PPD) will be positive in 50 to 97 percent of pa-
tients with GI tract TB. Colonoscopy with biopsy is
necessary for histologic or microbiologic confirma-
tion. Histologically, granulomas may be present or
absent in both TB and Crohn’s, these are classically
caseating in TB. PCR is a good diagnostic test when
used on biopsy specimens. Endoscopic fine needle
aspiration cytology that demonstrates acid-fast ba-
cilli may be a useful technique when submucosal
involvement is present. Empiric treatment may
be needed in some cases. It can be challenging to
distinguish intestinal TB from Crohn’s disease. In
a metaanalysis Bayesian model, factors were iden-
tified that helped to distinguish them. Those favor-
ing TB included transverse ulcers on colonoscopy,
a patulous ileocecal valve, fever, night sweats and
ascites among others. Those favoring Crohn’s dis-
ease included longitudinal ulcers on colonoscopy,
mucosal bridges, rectal involvement and perianal
disease, among others.17
Parasites
Parasites can cause a variety of symptoms (Table
11.3).
Amebiasis
Entamoeba histolytica exists in 2 forms: an in-
fectious cyst and an invasive trophozoite and can
cause a wide range of disease, ranging from asymp-
tomatic carriage (90 percent, after which sponta-
neous clearing is frequent) to severe dysentery (10
percent). In the US, dysentery is less common than
mild symptoms of colicky abdominal pain and di-
arrhea that may alternate with constipation, thus
mimicking IBS. The ingested cysts release tropho-
zoites in the terminal ileum. The trophozoites then
penetrate the colonic mucosa, most commonly in
the cecum and ascending colon and can cause deep
ulceration. Hematogenous spread to the liver can
cause liver abscesses. Non-pathogenic strains such
as E dispar are very common in men who have sex
with men. Other nonpathogenic amebae include
Entamoeba coli, Entamoeba hartmanni, Endo-
limax nana, and Iodamoeba buetschlii and their
presence in stool may indicate ingestion of con-
taminated food or water. The incubation period is
3 weeks but can be up to 4 months so travelers may
develop symptoms long after exposure. The typical
symptoms are diarrhea, abdominal pain and fever.
Complications include colonic strictures, perfora-
tion, extra intestinal infection such as liver abscess
(especially in the right lobe of the liver), brain or
lung abscess.
 Chapter 11 — GI infections of the small intestine and colon
Stool exam is the initial diagnostic test, but is
not very sensitive. Other stool tests include an ELI-
SA test, immunofluorescent assay, indirect hemag-
glutination, and PCR. Some consider biopsy to be
the gold standard. Serology (which is positive in 75
to 85 percent of patients with acute amebic colitis)
is helpful to diagnose invasive amebiasis, as it will
be negative in E dispar and positive in E histolyti-
ca, but of course results will be delayed.
Treatment is recommended for all patients,
even those who are asymptomatic as they can still
spread infection. The preferred regimen is metro-
nidazole for the invasive trophozoites with dilox-
anide furoate or paromomycin. Eradication should
be confirmed with follow-up stool tests.
Balantidium coli
This is the only ciliate that infects humans (it usually
infects pigs). It is usually asymptomatic but may cause
acute colitis. Symptoms include bloody diarrhea, ab-
dominal pain, nausea, and vomiting and weight loss.
Rare cases of chronic colitis have been described,
with resolution after tetracycline therapy. Diagnosis
is made by finding cysts or trophozoites in the stools.
Blastocystis hominis
This organism, originally classified as yeast, is now
recognized to be a parasite and its pathogenicity has
long been the subject of debate. Its presence in the
stools of asymptomatic individuals (such as cafete-
ria workers being screened) argues against pathoge-
nicity. However, multiple case reports of individu-
als with diarrhea and large numbers of organisms
in their stools who respond to treatment, argue for
its role as a pathogen. Some suggest that symptoms
may only occur with a high number of organisms,
ie, more than 5/high-power microscopic field. Typi-
cal symptoms are diarrhea, abdominal pain, nausea,
vomiting, malaise and flatulence.
One reasonable approach is to treat when
present in any immunocompromised individuals;
treatment is also reasonable in immune competent
individuals if other causes of diarrhea are not ob-
vious or have been eliminated. However, response
to therapy may be due to eradication of other un-
detected pathogens and there is no evidence that
379
it changes the natural history. Treatment is met-
ronidazole, paromomycin, or trimethoprim sul-
famethoxazole (TMP/SMX). One report showed
efficacy of nitazoxanide in resolution of persistent
diarrhea associated with B Hominis, supporting its
pathogenicity.18
Trichuris
Trichuris trichiura, also known as whipworm, is a
common nematode infection. It is estimated that
25 percent of the world population harbors this
parasite. Transmission is fecal-oral in areas with
poor sanitation and hygienic practices. The main
symptom is diarrhea. With a large worm burden
(ie, more than 200 worms), colitis and dysentery
with bloody diarrhea can occur. Rectal prolapse is
frequently seen. Diagnosis is made by stool exam.
Eosinophilia is present in 15 percent. Treatment is
metronidazole or albendazole.
Viral colitis
Herpes simplex virus II (HSVII)
HSVII can cause distal proctitis, usually acquired
from receptive anal intercourse with an infected
individual. Typical symptoms include severe anal
pain and discharge, sometimes associated with
urinary retention and/ or constipation. Diarrhea is
uncommon. Diagnosis is best made by culture of
anal swabs or skin lesions, but sigmoidoscopy and
biopsy can be helpful. Treatment with acyclovir or
valacyclovir is usually effective.
Cytomegalovirus (CMV)
CMV infection is common with immunosuppres-
sion, but cases of self-limited colitis have been re-
ported. These cases were diagnosed when CMV
intranuclear inclusion cells were found in biopsies;
therapy is not necessary in self-limited disease. In
immunocompromised patients, biopsy for viral cul-
ture is also recommended and treatment with an
antiviral agent such as ganciclovir. The association
of CMV and IBD is discussed later in this chapter.
Fungi
Most fungal infections occur in immunocmpromised
patients, with the exception of histoplasmosis, which
380 Digestive Diseases Self-Education Program®
can involve the colon and small intestine, as well as
other areas of the GI tract when it disseminates.
Paracoccidioidomycosis
In South America, Paracoccidioidomycosis (South
American Blastomycosis) can cause a granuloma-
tous inflammation resembling Crohn’s disease. In
both of these infections, organisms can be recog-
nized in biopsy specimens.
Candida albicans
Candida albicans occurs ubiquitously but can
be invasive in immunocompromised patients, in
whom colonic ulcers have been described. Fungal
infections are uncommon in immunocompetent
individuals. Candida may be found in the stools of
asymptomatic individuals. There are a few case re-
ports of otherwise healthy individuals with chronic
diarrhea, and Candida in their stools whose symp-
toms resolved with a short course of nystatin.
Microsporidiosis
Microsporidiosis (previously considered a parasite
but now classified as fungi) Microspora are spore-
forming organisms that have, as a group, been rec-
ognized as pathogenic in immunocompromised
individuals, especially those with HIV infection.
However, cases also occur in immunocompetent
individuals. Multiple species infect humans; 2 that
involve the gut are Enterocytozoon bieneusi and
Encephalitozoon intestinalis. Symptoms are wa-
tery diarrhea, abdominal pain, malnutrition, nau-
sea and vomiting.
Diagnosis is made by finding spores in the
stool. PCR is promising as a diagnostic test. Treat-
ment is albendazole or fumagillin.
Special syndromes
Food poisoning
The worldwide distribution of food has led to out-
breaks that can occur many thousands of miles
from the source of the contaminated food. In the
US, food-borne illnesses cause 5000 deaths annu-
ally and 324,000 hospitalizations. Those at greatest
risk are the very young, very old, and immunocom-
promised. The most common cause is norovirus;
other causes are Campylobacter jejuni (raw poul-
try). Oher common causes include STEC 0157:H7
infection due to contaminated ground beef and
unpasteurized apple juice, Cyclospora infection
associated with imported raspberries, and Listeria
monocytogenes with lunch meats and cantaloupes.
Two marine toxins can cause illnesses: scom-
broid poisoning and ciguatera reef poisoning.
Scombroid poisoning is an allergic histamine re-
action from eating improperly refrigerated fish;
naturally occurring histidine changes to histamine
as fish decomposes. Scombroid poisoning is not fa-
tal and usually follows consumption of fin fish (eg,
tuna, mahi mahi). In contrast, ciguatera reef fish
poisoning can be fatal. Predatory reef fish such as
barracuda or moray eels may accumulate a toxin
that causes gastroenteritis and neurological symp-
toms, including altered sense of taste, hot and cold
paresthesias, and nerve palsies. In the Caribbean,
GI symptoms typically precede neurologic symp-
toms. There are no diagnostic tests and no therapy.
In 20 percent, the symptoms may last for months.
Traveler’s diarrhea
Traveler’s diarrhea is a significant problem world-
wide, estimated at 9 million cases per year. The risk
of development is associated with the country vis-
ited: generally, Africa and the Middle East have a
high risk, while the Caribbean and parts of South
America have an intermediate risk. Organisms
are generally acquired by the fecal-oral route from
contaminated food and water, thus care in diet can
decrease one’s risk. Risk is higher with decreased
stomach acid from gastric surgery or medications.
There may be a genetic predisposition. Traveler’s
diarrhea is most common in the first week (90
percent) and second week of travel, particularly in
rainy seasons and summer months.
The most common clinical syndrome consists
of abdominal cramping, bloating, malaise, and wa-
tery diarrhea. The typical illness lasts 24 hours, but
the course can last 4 to 5 days or up to a week. A
minority (5–10 percent) will have dysentery with
blood and tenesmus. Rarely (2 percent) diarrhea
 Chapter 11 — GI infections of the small intestine and colon
will last longer than a month.
ETEC and norovirus cause the majority of trav-
eler’s diarrhea, which is most common in those who
go to areas with poor hygiene. The most common
bacterial causes in American travelers are ETEC and
EAEC (40–60 percent of cases), Shigella, and Salmo-
nella. Campylobacter accounts for 10 to 25 percent
of cases. Less common are Yersinia, noncholera Vib-
rios, Aeromonas, and Plesiomonas. Parasites caus-
ing traveler’s diarrhea are usually protozoa: Giardia,
Amoeba, Cryptosporidia, and Cyclospora. No patho-
gen is identified in up to 20 percent of cases.
Prophylaxis with bismuth subsalicylate (2 tablets
with meals and at bedtime, for a total of 8 tablets daily)
provides protection rates of 40 to 65 percent.
Protective rates with rifaximin are 70 percent.
The most effective prevention is being careful about
the food and beverages that one consumes. A general
rule is “boil it, cook it, peel it, or forget it.” Even ice
cubes made with contaminated water transmit patho-
gens that can cause diarrhea. Moist room-tempera-
ture foods pose the highest risk. Travelers who visit
family are at higher risk than those who stay in hotels.
New guidelines recommend prophylaxis with
bismuth subsalicylate (BSS). Antibiotics should not
be used for prophylaxis, except in those at high risk
of health related complications, in whom rifaximin
is recommended. Treatment of mild traveler’s di-
arrhea is with BSS or loperamide. Loperamide has
been shown to decrease symptoms and duration of
illness, and is safe in the absence of severe dysen-
tery, but should not be given if STEC is suspected.
Antibiotics should only be given to those with mod-
erate diarrhea, and include azithromycin or a fluo-
roquinolone (as long as resistance rates are not too
high in the area). Rifaximin can be given, but not
if an invasive pathogen is likely. For severe diar-
rhea, azithromycin is recommended first line and is
the drug of choice for children age 2 to 8, as well as
for pregnant women. In those with persistent diar-
rhea (2-4 weeks), or in whom empiric therapy has
failed, microbiologic testing is indicated.
Infections and IBD
GI infections can play a role in IBD in different
ways. Most important is the increase in CDI in IBD
381
patients, with an increase in morbidity and mortal-
ity greater than with IBD alone or CDI alone. Risk
factors are colon disease and immune suppression.
Patients with IBD may develop
CDI without preceding antibiotic exposure.
Expert opinion recommends testing for C difficile
in all patients with flare, inpatient or outpatient, in
pouchitis, and when IBD is not responding. Experts
also recommend using vancomycin for initial ther-
apy, even in mild disease, and hold an increase in
immune suppressive therapy for a few days while
the infection is being treated.10 These patients are
challenging to manage, because CDI and IBD not
only have similar symptoms, but can fuel each oth-
er. Consultation with an IBD expert is strongly
recommended, particularly as recurrent CDI in a
patient with IBD increases the risk of colectomy.
Most experts still recommend testing for other en-
teric pathogens in IBD patients who have a flare,
although the yield of stool cultures during an IBD
flare may be as low as 5 to 20 percent. Bacterial
superinfections reported include Campylobacter,
Salmonella, Shigella, STEC, Aeromonas, Plesi-
omonas and Listeria. A recent retrospective review
showed that fewer than 3 percent of patients had a
non-C. difficile infection, however.21
The role of CMV in IBD, especially in ulcerative
colitis, is of great interest. It is well known that CMV
reactivation occurs with immune suppression after
organ transplant and with HIV infection, among
other scenarios. Moreover, CMV can occasionally
cause colitis, even in immunocompetent individu-
als. In patients with ulcerative colitis, superinfection
with CMV has been reported in series and case re-
ports, and has been felt to cause poor outcomes and
increased need for colectomy. While some feel that
CMV found in colonic biopsies is incidental, there is
increasing evidence that it can worsen the course of
the disease. Diagnosis of CMV in biopsy specimens
should not be limited to finding CMV inclusion cells,
but should include additional testing on tissue, such
as shell vial culture or PCR for CMV DNA. Positive
CMV culture from blood does not correlate well with
gut infection. Treatment with ganciclovir or other
appropriate agents should be given, as this can re-
sult in clinical improvement. CMV colitis should es-
382 Digestive Diseases Self-Education Program®
pecially be suspected in steroid-refractory IBD, as
it has been detected in 20 to 36 percent of these
cases. Its occurrence in ulcerative colitis appears
higher than in Crohn’s disease.
Parasitic coinfections in IBD are relatively un-
common, but can have disastrous consequences if
they are not recognized and the patient receives im-
munosuppressive therapy. There are case reports
of fatal amebiasis in patients with ulcerative colitis
given steroids, and hyperinfection syndrome with
Strongyloides can also be serious or fatal.
Diagnosis of acute diarrhea
The evaluation of acute diarrhea starts with obtain-
ing a detailed history, including inquiry about recent
travel, food-born triggers, sick contacts, antibiotics,
occupational exposures and recent hospitalizations.
Physical exam should evaluate for volume depletion
and abdominal tenderness. For most mild to moder-
ate symptoms, no further evaluation is indicated. In
the hospital setting, patients who develop diarrhea
after 3 days of admission usually do not need testing
for enteric pathogens other than C difficile.
Findings of white blood cells and fecal leuko-
cytes in the stool are nonspecific, as they can be
negative, and cannot distinguish infectious diar-
rhea from other inflammatory diarrhea. Newer
stool markers such as fecal lactoferrin and particu-
larly fecal calprotectin have emerged as adjunctive
tools in the diagnosis and monitoring of IBD. How-
ever, these are also nonspecific and may be positive
in infectious diarrhea as well.
Recent guidelines advise stool culture when
there is moderate to severe watery diarrhea with
no travel history and fever greater or equal than 101
for more than 72 hours.22 When there is dysentery,
ie, bloody diarrhea, stool culture is indicated un-
less there is travel history and patient has fever, in
which case empiric antibiotics are indicated. Cul-
ture is also indicated if there are signs of sepsis,
fever or severe abdominal pain. Blood cultures are
indicated in infants, sepsis, immunocompromised
patients and other high risk individuals, such as
those with hemolytic anemia.23 STEC 0157 can be
detected by culture, but the non-0157 strains are
best detected by Shiga toxin or genome assays.
Stool evaluation is also indicated in persistent
diarrhea or if there is concern for an epidemic, or
if the person works in food handling, hospital, or
LTCF. In the US, routine stool culture will detect
Campylobacter, Salmonella, and Shigella, though
most labs will also screen for STEC. If there is sus-
picion for other specific pathogens, the lab should
be notified as sometimes certain culturing tech-
niques need to be employed.
Diagnosis of parasites has traditionally depend-
ed on microscopic detection. Improved methods for
detection of some parasites are now available, but
are more expensive. Monoclonal anti-Giardia lam-
blia antibody stains detect cysts in stool and may
double the yield of standard microscopy. Giardia an-
tigen in stool can be detected with commercial EIA
kits with a sensitivity of 95 percent and specificity
of 100 percent. Similar tests are available for Cryp-
tosporidium. Testing 1 or 2 specimens by EIA tests
for Giardia or Cryptosporidium has a sensitivity
greater than 95 percent and is better than direct mi-
croscopy. The advantage of direct microscopy is the
ability to detect different organisms. The advantage
of kits is improved detection of a specific organism.
An emerging area of diagnosis is the use of mul-
tiplex GI PCR panel tests. These culture-indepen-
dent tests are rapid, but expensive. They can test
for multiple pathogens, both bacteria and parasites
with one stool sample. Several are FDA approved
and can test for 12-20 pathogens depending on the
test used. In one series, the yield was higher than
standard culture, 35 percent versus 6 percent.24 They
can allow faster diagnosis and earlier treatment, es-
pecially in cases of food-borne illnesses. However,
they do not identify antibiotic resistant strains.
The CDC recommends follow up culture if public
health reporting is needed. Moreover, these panels
do not distinguish between carrier state and active
infection. Arguments for use of these panels include
quicker access to treatment, implementation of in-
fection control measures in hospitals, and a possible
decrease in associated antibiotic and/or laboratory
testing costs.25 Limitations of their use are knowing
which pathogens should be included (ie,C difficile)
and interpretation of positive results.
 Chapter 11 — GI infections of the small intestine and colon 383

tute. Common sports drinks should be used with

Computed tomography scans and
caution as oral rehydration solutions, because the
colonoscopy
amount of electrolytes such as sodium and potas-
If there is suspicion for colitis, such as in the pa-
sium are not adequate to replace the losses from
tient with abdominal pain, fever, or abnormal ab-
more severe diarrhea. They may also contain ex-
dominal exam, then cross-sectional imaging of the
cessive sugar, which can worsen diarrhea. Some
abdomen with computed tomography (CT) scan
antidiarrheal agents can be safely used (bismuth
may be indicated. Colon wall thickening can be
subsalicylate,
seen with infection but also with IBD and ischemia.
loperamide) in most infectious diarrheas.
Colonoscopy may confirm colitis, document loca-
These agents should not be used in children (they
tion, determine severity, and facilitate biopsy.
may increase the risk of hemolytic uremic syn-
Colorectal mucosal biopsy is often, but not
drome in STEC), in adults with severe colitis when
always, helpful in differentiating acute infectious
toxic megacolon could occur, or with C difficile di-
colitis from IBD. In the former, crypt architecture
arrhea. Zinc supplementation improves the course
is usually normal, and lamina propria inflamma-
of acute diarrhea in children. Transient lactose in-
tion is more marked in the upper third of the muco-
tolerance can also occur with acute infectious diar-
sa. Crypt abscesses and giant cells are nonspecific
rhea involving the small intestine.
and can occur in infectious colitis as well as IBD.
In contrast, crypt architecture is often abnormal in
IBD, with crypt distortion the most frequent find-
Antibiotics
For travel related acute diarrhea, empiric anti-
ing. Crypt distortion includes branched glands and
biotics are recommended for moderate to severe
a villous surface. Lamina propria inflammation is
watery diarrhea, and severe dysentery. Specific
present with an increase in both acute and chronic
antibiotics are quinolones, azithromycin or rifaxi-
inflammatory cells. Basal plasmacytosis, basal lym-
min, but do not use the latter if an invasive patho-
phoid aggregates, and basal lymphoid hyperplasia
gen is suspected.
are also more common in IBD.
For non-travel related moderate watery diar-
Isolated proctitis can also occur in sexually
rhea with fever that has lasted more than 72 hours,
transmitted infections, particularly those transmit-
microbiologic assessment and consideration of em-
ted through receptive anal intercourse. This can in-
piric treatment with azithromycin is recommended.
clude gonorrhea, HSVII, syphilis, and chlamydia.
Patients with dysentery should undergo microbio-
Other bacterial agents such as Salmonella, Shigel-
logical assessment and directed therapy, as should
la, and Campylobacter can cause proctitis. These
those with persistent (2-4 weeks) diarrhea.
findings on colonoscopy or flexible sigmoidoscopy
can mimic IBD, sometimes with discrete ulcer-
ations or anal fissures as with syphilis. Biopsy can
CT scans and colonoscopy
If there is suspicion for colitis such as in the patient
be helpful to distinguish from IBD.
with abdominal pain, fever, or abnormal abdomi-
Certain infections will have characteristic his-
nal exam then cross sectional imaging of the ab-
tologic findings, as listed below in Table 11.4.
domen with CT scan may be indicated. Colon wall
thickening can be seen with infection but also with
IBD and ischemia. Colonoscopy may confirm coli-
Therapy of acute diarrhea tis, document location, severity and allow biopsy.
Oral rehydration is the first step, unless the se- Colorectal mucosal biopsy is often but not al-
verity of illness calls for IV fluids. An inexpensive ways helpful in differentiating acute infectious
recipe for oral rehydration solution is ½ tsp salt, colitis from IBD. In the former, crypt architecture
½ tsp baking soda, and 4 Tbsp sugar in 1 L water. is usually normal and lamina propria inflamma-
Diluted fruit juice and saltines are a good substi- tion is more marked in the upper third of the mu-
384 Digestive Diseases Self-Education Program®
Table 11.4
Histology of infectious colitis
Characteristic histology
• Preservation of normal histology
• Acute inflammation, often superficial (upper one-third of lamina propria)
• Crypt abscesses
Specific diagnostic finding
Pseudomembranes
Viral inclusions
• Intranuclear and/or
• Intracytoplasmic
• Intranuclear
Parasites
• Diagnostic organism on surface of biopsy
Granulomas, organisms visible within
Granulomas
cosa. Crypt abscesses, giant cells, are non-specific
and can occur in infectious colitis as well as IBD.
In contrast, crypt architecture is often abnormal in
IBD, with crypt distortion the most frequent find-
ing. Crypt distortion includes branched glands and
a villous surface. Lamina propria inflammation is
present with an increase in both acute and chronic
inflammatory cells. Basal plasmacytosis, basal lym-
phoid aggregates, and basal lymphoid hyperplasia
are also more common in IBD.
Isolated proctitis can also occur in sexually
transmitted infections, particularly those transmit-
ted through receptive anal intercourse. This can in-
clude gonorrhea, Herpes Simplex Virus II (HSV II),
syphilis and chlamydia. Other bacterial agents such
as salmonella, shigella and campylobacter can cause
proctitis. These findings on colonoscopy or flexible
sigmoidoscopy can mimic IBD, sometimes with dis-
crete ulcerations or anal fissures as with syphilis. Bi-
opsy can be helpful to distinguish from IBD.
Certain infections will have characteristic his-
tologic findings, as listed below in Table 11.4.
C. difficile
(E. coli 0157:H7-less common)
Ischemic colitis
Cytomegalovirus
Herpes simplex virus type 2
Entamoeba histolytica
Cryptosporidium
Schistosomiasis
C. trachomatis
Syphilis
Tuberculosis
Infectious causes of persistent
or chronic diarrhea
When diarrhea lasts longer than two to four weeks,
infection is less likely but some pathogens still
bear consideration. Parasites are more common
than bacteria in these cases, and so the first step
in evaluation is often stool exam for ova and para-
sites. Bacteria that can cause chronic infections are
rare but include E. coli, Aeromonas and C. jejuni.
Chronic symptoms are more often due to parasitic
infection such as Giardia, Cryptosporidium, I. belli,
and Cyclospora. Entamoeba histolytica is uncom-
mon in the U.S. but commonly acquired in travel to
developing countries. Blastocystis hominis is seen
in stools from patients with diarrhea, but it is not
clear whether it is a true pathogen. Other causes of
chronic diarrhea include EPEC, Aeromonas, Yer-
sinia enterocolitica, and recurrent Clostridium dif-
ficile. Tuberculosis has a predilection for ileocecal
involvement and its symptoms are more typically
chronic than acute. Epidemic chronic diarrheal
 Chapter 11 — GI infections of the small intestine and colon 385

syndromes as described in Brainerd, Minnesota,
and Henderson County, Illinois, suggest infectious
organisms not yet identified.
Diarrhea that persists after infection may also
be from post-infectious IBS or new onset IBD and
not true chronic infection. Infectious diarrhea is
becoming increasingly recognized as a trigger for
IBS. It was first described as “post-dysenteric” IBS
in 1962 by Chaudhary and Truelove. Several re-
cent prospective studies have identified post-in-
fectious IBS in four to 30 percent of patients after
one year depending upon the study. Risk factors
for post-infectious IBS include: severity of the ini-
tial illness, female gender, and psychological fac-
tors (in some but not all studies). Forty percent
will have resolution of symptoms at five years.
Post-infectious IBS can occur after either bacterial
or viral infection.
Other sequelae of infection include functional
dyspepsia, constipation, and GERD.
ral interaction with ACE2 can lead to dysbiosis,
inflammation, and associated GI symptoms.28,29
SARS-CoV-2 has been detected in endoscopic bi-
opsies from throughout the GI tract.30
Although SARS-CoV-2 RNA can be isolated
from approximately 50% of stool samples of in-
fected patients, this does not necessarily correlate
with the presence of GI symptoms or persistent in-
fectivity.31 Live SARS-CoV-2 has been detected on
electron microscopy in stool samples, raising the
possibility of fecal-oral route of transmission as an
alternate route of infection, but evidence for this
has not been demonstrated.32
Patients with GI symptoms have been shown
to manifest more severe disease with a poorer
prognosis. Theories regarding causality include
bacterial translocation within the gut, electrolyte
disturbances, and delay in care due to unrecog-
nized COVID-19 disease in patients with predomi-
nantly GI symptoms.33,34

Diarrhea due to non-GI

infections
Non-GI infections that can cause diarrhea include
sepsis, bacterial or viral pneumonia, HIV, severe
acute respiratory syndrome, brucellosis, leptospi-
rosis, Dengue fever, and Lyme disease. 26

SARS-CoV-2 infection
Patients infected with the severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) during the
Coronavirus Disease 2019 (COVID-19) pandemic
commonly exhibit GI symptoms. These can in-
clude diarrhea, nausea, vomiting, and transami-
nitis. COVID-19–related GI symptoms can occur
before, concurrently, or in the absence of respira-
tory symptoms.
The angiotensin converting enzyme 2 (ACE2)
receptor is the primary route for cellular invasion
by SARS-CoV-2, through interaction with the vi-
ral transmembrane spike protein (S protein).
Although widespread within the body, ACE2 is
expressed highly in lung AT2 cells, as well as vari-
ous areas of the GI tract, particularly the luminal
surface of small intestinal enterocytes. This vi-
386 Digestive Diseases Self-Education Program®
Pearls and pitfalls
of the board exam
• Small intestinal pathogens, viruses (like
Norovirus and Rotavirus) bacteria (like
Enterotoxigenic E. coli [ETEC]) and
parasites (like Giardia, Cryptosporidium)
are generally noninvasive so they do not
cause bloody diarrhea.
• Ileocolonic pathogens, predominantly
bacteria like Campylobacter, Shigella,
Salmonella and Shiga toxin E coli (STEC)
can be invasive and thus cause bloody
diarrhea.
• Antidiarrheals and antibiotics are
contraindicated STEC and suspected
STEC as they increase the risk of hemolytic
uremic syndrome (HUS).
• The most common causes of HUS are
Shigella and STEC infections.
• Food poisoning with initial nausea and
vomiting is typically due to a preformed
toxin such as S aureus (typically dairy
products) B cereus (typically fried rice) or
C perfringens (typically gravies)
• STEC like 0157:H7, is an
enterohemorrhagic E. coli that produces a
cytotoxin and does not invade the colonic
mucosa. In contrast, ETEC also produces a
toxin (enterotoxin),
but does not invade the mucosa.
• Headache and meningismus in a
patient with diarrhea should raise
suspicion for Listeria monocytogenes
infection. Pregnant women and
immunocompromised individuals are at
increased risk, and there is increase in fetal
and maternal mortality. Blood culture may
have the highest yield.
• Eosinophilia is more common with hel-
minth infections than protozoal infections.
• Strongyloides hyperinfection (dissemi-
nated disease) occurs in immunocom-
promosed patients. Eosinophilia may be
absent. This has a high mortality if not
recognized and treated.
• Quinolones are not a wise choice to treat
traveler’s diarrhea in Southeast Asia due
to increased rates of quinolone resistant
Campylobacter.
• Azithromycin, single dose, is effective for
treatment of acute traveler’s diarrhea,
and is a safe alternative to quinolones for
children and pregnant women.
• There is no perfect diagnostic test for C
difficile infection (CDI). Even polymerase
chain reactionfor Toxin B can occasion-
ally be negative in true infections. Empiric
therapy is reasonable for patients with
suspected CDI and severe symptoms.
• Severe/ fulminant CDI requires therapy
with oral vancomycin and intravenous
metronidazole and close monitoring; per
rectum vancomycin should be added if
severe ileus is present.
• A patient with severe CDI, as evidenced
by increased white blood count, elevated
serum creatinine, a lower albumin, abdom-
inal distension, requires maximal medical
therapy and early surgical consultation, as
well as consideration of fecal microbiota
transplant (FMT). Antibiotic regimes are
less effective in recurrent CDI. FMT offers
higher cure rates in these patients.
• Yersinia and tuberculosis infections cause
ileocolitis and mesenteric adenitis that can
mimic Crohn’s disease or appendicitis.
• Diarrhea and arthritis: think of Yersinia or
Whipple’s disease
• Recurrent giardiasis is common with im-
mune deficiency, such as IgA deficiency,
which should be ruled out.
• Salmonella infection has a hematogenous
phase so one can get distant infections of
grafts, and joints.
• There is no long-lasting immunity to
norovirus.
 Chapter 11 — GI infections of the small intestine and colon
Most efficient source
reviews for examination
preparation
• Dupont HL. Acute Infectious Diarrhea in Immu-
nocompetent Adults. N Engl J Med. 2014 Apr
17;370(16):1532-40. An excellent overview, clin-
ically relevant, addresses evaluation including
guidelines for stool culture, and has an excellent
table of summarizing diagnostic method and
therapy for the most common organisms. Some
may like the algorithm for evaluation of patients
with severe diarrhea, that stratifies patients
into, one of 4 groups, colitis, fever, exposure to
antibiotics, in a hospital or LTCF and persistent
diarrhea (14-30 days duration)
• Aboutaleb N, Kuijper EJ, van Dissel JT. Emerging
infectious colitis. Curr Opin Gastroenterol. 2014
Jan;30(1):106-15. An excellent review of organ-
isms that cause colitis, as well as most common
causes of food-borne illness. A table summa-
rizes recent outbreaks of the most common
pathogens, including country, number of cases,
vehicles and mentality.
• Riddle MS, DuPont HL, Connor BA. ACG Clinical
guideline: diagnosis, treatment and preven-
tion of acute diarrheal infection in adults. Am J
Gastroenterol 2016;111:602-622.
• Shane AL, Mody RK, Crump JA et al. 2017 Infec-
tious diarrhea IDSA clinical practice guidelines
for the diagnosis and management of infectious
diarrhea. Clin Infect Dis. 2017; 65: 45-80.
• McDonald LC, Gerding DN, Johnson S et al.
Clinical Practice Guidelines for Clostridium diffi-
cile infection in adults: 2017 update by the IDSA
andSHEA. Clin Infect Dis 2018; 66:1-48.
• Riddle MS, Connor BA, Beeching NJ et al.
Guidelines for the prevention and treatment of
travelers’ diarrhea: a graded expert panel. J
Travel Medicine 2017; 24 suppl 1: S63-80.
• Surawicz CM, Brandt LJ, Binion DG, et al. Guide-
lines for diagnosis, treatment, and prevention of
Clostridium difficile infections. Am J Gastroen-
terol 2013;108(4): 478-98..
• Zollern-Schwetz, Krause R. Therapy of acute
gastroenteritis role of antibiotics. Clin Microbiol
Infect 2015;1-6. Provides guidance on indica-
tions for empiric antibiotic therapy in infections,
gastroenteritis.
387
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390 Digestive Diseases Self-Education Program®