Download Guideline for the management of acute diarrhea in adults

Journal of Gastroenterology and Hepatology (2002) 17 (Suppl.) S54–S71
WORKING PARTY REPORT
Guideline for the management of acute diarrhea in adults
SATHAPORN MANATSATHIT,* HERBERT L DUPONT, † MICHAEL FARTHING, ‡
CHOMSRI KOSITCHAIWAT, § SOMCHAI LEELAKUSOLVONG, * BS RAMAKRISHNA, ¶
ADERBAL SABRA,** PETER SPEELMAN †† AND SURAPOL SURANGSRIRAT ‡‡
*Division of Gastroenterology, Siriraj Hospital, §Division of Gastroenterology, Ramathibodi Hospital,
‡‡
Division of Gastroenterology, King Pramonkut Hospital, Bangkok, Thailand, †St. Luke’s Episcopal Hospital,
Houston, Texas, **International Center for Interdisciplinary Studies of Immunology, and Department of
Pediatrics, Georgetown University Medical Center,Washington DC, United States of America, ‡Faculty of
Medicine, University of Glasgow, Glasgow, United Kingdom, ¶Department of Intestinal Science, Christian
Medical College and Hospital,Vellore, India, ††Amsterdam Medical Center, Amsterdam, The Netherlands
INTRODUCTION
Acute diarrhea in adults is one of the most common
diagnoses in general practice,1,2 and is responsible for
considerable morbidity around the world.3–5 While
acute diarrhea is perceived as a major cause of childhood mortality in developing countries, adult mortality
from diarrhea is also not uncommon particularly during
epidemics of diarrhea. Contaminated food and water,
together with unhygienic eating habits, account for the
continuing high prevalence of acute diarrhea in adults.
In industrialized countries, the incidence of acute
diarrhea is estimated to average 0.5–2 episodes per
person per year, and the corresponding figure could be
much higher in developing and underdeveloped countries. In the USA, with a population of around 200
million, about 99 million episodes of acute diarrhea
occur every year in adults. Twenty-five percent of hospitalizations in the USA were due to diarrhea and 85%
of the mortality associated with diarrhea occurred in the
elderly (> 65 years old).6 It accounts for a large amount
of economic loss and a waste of a country’s resources
and labor forces in caring for this group of patients.7 It
is hoped that the development of this guideline will be
able to provide measures for general practitioners and
health care workers around the world to effectively care
for adult diarrhea patients so that the mortality and
complications can be minimized.
Algorithm and definition
The final algorithm that was developed for the management of adult diarrhea was the result of intensive
discussion among the experts. It particularly emphasized simplicity, feasibility and availability of options.
It tries to be as general as possible without sacrificing
the basic principles and theoretical background of
sound management. The algorithm, in itself, should
provide a complete document that would be applicable
to the case management of diarrhea. However, some
explanation and amplification is necessary to clarify the
terms and phrases that have been used, as well as to
explain the basis for certain decision pathways in the
algorithm.
Adult: The definition of ‘adult’ varies from one
country to another. As applied in this guideline, the
term ‘adult’ refers to someone who is of age 12 years or
above.
Acute diarrhea: This is defined as the passage of three
or more than three loose or watery stool in 24 h, or
passage of one or more bloody stool. Acute diarrhea
refers to illness not lasting longer than 14 days.
Other conditions that may present as acute diarrhea: ‘Acute diarrhea’ is a clinical syndrome that is
commonly understood to refer to infective gastroenteritis. However, as defined, acute diarrhea may be a
symptom of other intra-abdominal or systemic illnesses.
These other clinical conditions may require particular
investigations and management, and will need to be
recognized and excluded at the outset. Careful history
and physical examination is necessary to exclude these
conditions from the commonly understood ‘acute diarrhea’. Special attention should be paid to exclude signs
of peritonism or peritonitis, which will indicate serious
illnesses that might require surgical care. Examples
of these diverse clinical conditions are presented in
Table 1.
Specific conditions of acute diarrhea that require
special consideration: Although the term ‘acute
diarrhea’ commonly refers to infectious, toxin-induced
and drug-induced diarrhea, there are specific acute
diarrhea syndromes that may need a specifically tailored
approach and management, and where the general algorithm may need to be modified. For example, during
epidemic acute diarrhea such as cholera, it is important
to quickly identify the organism in the first patients presenting with illness, and to initiate public health mea-
Correspondence: Dr S Manatsathit, Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol
University, Bangkok, Thailand. Email: [email protected]
© 2002 Blackwell Science Asia Pty Ltd
Acute diarrhea in adults
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Acute Diarrhea (< 14 days)
Other conditions which
may present as acute
diarrhea (see Table 1)
History & PE
Major Presentation
Specific diarrhea requiring special consideration
- Acute diarrhea in the elderly (age > 65 years)
- Traveler’s diarrhea
- Antibiotic associated enterocolitis
- Hemorhagic colitis (due to EHEC or STEC)
- Outbreak diarrhea
- Other specific conditions (see Table 2)
Toxin induced food poisoning
or viral gastroenteritis
Vomiting
Replace deficit with ORS/IVF
Maintain hydration with ORT
Diarrhea
∑ Replace deficit with ORS/IVF
∑ Maintain hydration with ORT
Yes
Watery Diarrhea
Bloody Diarrhea
Clinical dehydration
Stool Examination,
culture/sensitivity1
E.histolytica
trophozoites
Metronidazole
plus cysticidal
drug
No
In Cholera-endemic area
Stool examination, DFM,*
Culture/Sensitivity
DFM +ve
ATB for
cholora
∑ Maintain hydration with ORT
∑ Consider antidiarrheals for 48 hrs.
DFM–ve,
wait for culture result
Consider ATB if
pathogen identified
If EHEC not suggested
Empiric ATB for 3–5 d.2
Not improved
Not improved
Stool examination,
Culture/Sensitivity
- Repeat stool examination
- Consider sigmoidoscopy/
colonoscopy + biopsy
Cured
Figure 1 Algorithm developed for the management of adult diarrhea. 1Stool examination and culture methods depend on
availability, affordability, and local practice of each community or country. 2Strongly recommended for severly ill patients (select
antibiotics according to sensitivity of local antibiogram). PE, Physical examination; DFM*, dark field microscopy (if not
available, look for ‘shooting bacteria’ under light microscopy); ATB, antibiotics; ORT, oral rehydration therapy; IVF, intravenous
fluid.
Table 1 Conditions presenting as acute diarrhea with or
without signs of peritonitis that should be excluded in a
patient presenting with acute diarrhea
Appendicitis
Adnexitis
Diverticulitis
Peritonitis secondary to bowel perforation
Systemic infections: for example malaria, measles, typhoid,
etc.
Inflammatory bowel disease
Ischemic enterocolitis
Mesenteric artery/venous occlusion
sures that will stop the outbreak. Acute diarrhea in the
elderly needs to be treated in a different manner from
that of younger people because of the possibility of complications relating to compromised cardiac and cerebral
circulation. A number of these clinical entities are listed
in Table 2, and these are discussed in greater detail in
the Appendix.
HISTORY AND PHYSICAL
EXAMINATION
Acute diarrhea is a complex symptom that may be
caused by any of a number of diseases, both infectious
and non-infectious. A proper history and physical
examination is therefore necessary in these patients.
Special attention should be paid to excluding
conditions that may require a different approach and
management.
History taking
In the history, it is essential to gather the following
information: age, onset and duration of diarrhea, character of the stool (watery, loose or bloody), frequency
and volume of stool, progression of severity of diarrhea,
presence and severity of vomiting, presence of fever, its
severity and duration, abdominal pain and its location
and character, cramps, and tenesmus. The severity of
diarrhea may be assessed in adults by the degree of disturbance of daily life and activities, debility, thirst, dizzi-
S56
ness, and syncope. The time of last urination should be
noted in patients with dehydrating diarrhea.
Occurrence of diarrhea after eating a contaminated
meal, the time interval between ingestion and development of diarrhea, and the occurrence of illness in others
who also partook of the meal are pointers to a bacterial cause of the illness.8 The source of water supply may
be helpful as evidence of a common-source outbreak.9
The location in which the patient develops diarrhea may
be predictive of the causative organism, for example at
home, in hospital or in an institution. History of recent
travel and the area travelled, may also be helpful. If
there is research to suggest that specific pathogens are
more common during a specific season, this is an additional factor of which to remain aware.
It is always worthwhile to exclude the non-infectious
causes of acute diarrhea and osmotic diarrhea, for
example drugs and toxins. One should inquire if the
patient has recently been taking medications or substances that can cause diarrhea, for example laxatives,
antacids containing calcium or magnesium, colchicines,
antibiotics, alcoholic beverages and sorbitol containing
gums. If such a history is obtained, the suspected
offending substance should be stopped before proceeding to any further evaluation.
In addition, it is important to take into account any
underlying diseases that may be present, such as diabetes, hypertension, heart disease, chronic lung disease,
chronic renal failure or cirrhosis, because these could
complicate the management of diarrhea. Any condition
that affects the patient’s immune status should be called
to the physician’s attention, such as practices that
may predispose the patient to HIV infection, history of
administration of immunosuppressive drugs, steroids,
and chemotherapy.
Physical examination
In the adult with diarrhea, it is important to look for
signs of dehydration, including examination of the
pulse, blood pressure (standing and sitting), jugular
venous pressure, skin turgor, mucosal dryness, for
example in the mouth and lips, evidence of sunken eye
balls and capillary filling.
It should be stressed that, regardless of the severity
of diarrhea, abdominal examination is strongly recommended for every patient. Both light and deep palpation should be carefully performed to exclude signs of
peritonitis. Although minimal tenderness to deep palpation can be found in dysentery, it should be seriously
observed and these patients must be closely monitored,
because some surgical or serious medical conditions, for
example appendicitis, diverticulitis, adnexitis, pancreatitis and ischemic colitis, may present as acute
diarrhea. In acute diarrhea, guarding, rigidity and rebound tenderness should not be present. If they are
present at all, further investigations and appropriate
measures should be taken.
Rectal examination should be part of the initial examination in every case, especially in patients over 50 years
of age.10 This allows the physician to see with certainty
S Manatsathit et al.
the character of stool and accurately assess the type of
diarrhea, whether it is watery or bloody. This is particularly helpful in situations in which patients, especially
the elderly or those with poor eyesight, might not be
able to give an accurate history.
MAJOR PRESENTATION: VOMITING
Diarrhoea is the predominating symptom in most
patients presenting as ‘acute diarrhea’. Having excluded
the other conditions listed in Tables 1 and 2, we are left
with a group of illnesses that comprise what is commonly understood as ‘acute diarrhea’.These are further
classified, on the basis of the stool character, as having
either watery diarrhea or bloody diarrhea. This is one
of the decision points in the algorithm, and is discussed
further. On the other hand, there are some patients with
‘acute diarrhea’ in whom vomiting overshadows
diarrhea as a symptom. In these patients, one should
suspect that the illness is caused either by food poisoning (induced by preformed bacterial toxin) or viral
gastroenteritis.
Bacterial toxin induced food poisoning
In patients with bacterial preformed heat-stable toxin
induced food poisoning, the incubation period is
usually 6–24 h, diarrhea occurs 2–7 h after eating the
contaminated food. These patients usually present with
intense nausea and severe vomiting as the major symptoms. Diarrhoea may follow and usually is not so severe.
Abdominal pain may also be present and is usually
colicky in nature. Most patients are afebrile and not
severely dehydrated unless vomiting or diarrhea is
intense. Clostridium perfringens is also a food-borne
disease with a characteristic incubation period of
8–14 h. C. perfringens differs clinically from food poisoning due to Staphylococcus aureus and Bacillus cereus
in the longer incubation period and in clinical symptoms. Vomiting is unusual in C. perfringens food-borne
disease and it is the most important clinical finding in
the other forms of food poisoning. Foods that are likely
to be contaminated with toxin or infectious organisms
Table 2 Specific acute diarrhea syndromes that require
special consideration
Acute diarrhea in the elderly (age ≥ 65-years-old)
Traveler’s diarrhea
Antibiotic associated enterocolitis
Hemorrhagic colitis (due to enterohaemorrhagic E. coli,
EHEC or Shiga-toxin producing E. coli, STEC)
Outbreak diarrhea
Acute diarrhea in immunocompromised hosts
Institutional diarrhea
Nosocomial diarrhea (hospital acquired)
Gay bowel syndrome
Acute diarrhea in septicemia prone conditions
Acute diarrhea in adults
are cake, bread and cooked rice that have been left for
a period of time. Bacteria that could produce such
toxins include S. aureus, B. cereus, C. perfringens, etc.
Most symptoms subside within 48–72 h.11 Symptomatic
and supportive treatment is usually sufficient. If the
patient can drink, oral rehydration therapy is highly
encouraged. If vomiting is severe and dehydration is significant, intravenous therapy may be necessary. Antiemetics, such as metocloparmide, are not effective if
given orally, but intramuscular injection may be efficient. Abdominal cramping pain may respond to antispasmodics, for example hyoscine, hyoscyamine and
dicyclomine.
Viral gastroenteritis
The Norwalk virus is the most common cause of viral
gastroenteritis in adults.12 However, rotavirus and other
viruses, for example astrovirus, calicivirus, coronavirus,
enterovirus, and small round virus-like particles, may
also be the cause. The illness has an incubation period
of between 18 and 72 h, and is characterized by the
abrupt onset of nausea and abdominal cramps followed
by vomiting and/or diarrhea. Low-grade fever (above
37.5°C or 99.5°F) develops in about half of affected
individuals. Headache, myalgias, upper respiratory tract
symptoms and abdominal pain are common. Red and
white cells are not normally found in the stool. The
illness is usually mild and self-limiting, lasting 24–48 h.
In some cases, diarrhea and vomiting may persist for a
week or longer.13 In general, oral rehydration treatment
is adequate and only in rare cases intravenous rehydration may be needed.14 Bismuth subsalicylate has been
shown to improve the clinical symptoms of viral
gastroenteritis.15
MAJOR PRESENTATION:
DIARRHEA
Watery diarrhea
Watery diarrhea, that is, stool of decreased form from
normal-looking, semiformed to loose or watery, without
the presence of blood, is often the clinical presentation
of enterotoxin induced diarrhea. Examples of such diarrhea include cholera caused by Vibrio cholerae andVibrio
O139, and diarrhea due to non-O1 vibrios, enterotoxigenic Escherichia coli, and enteropathogenic E. coli.
Some cases of infection with Vibrio parahemolyticus,
Salmonella, Aeromona spp., Pleisiomona spp., Campylobacter jejuni, Yersinia enterocolitica and Clostridium difficile may also present as watery diarrhea, especially in
the initial stages of their course (see Table 3).
S57
Table 3 Enteropathogens responsible for infectious diarrhea
(modified from Farthing M.)
Enteropathogen
Viruses
Rotavirus
Enteric adenovirus (types 40,41)
Caliciviruses
Astrovirus
Cytomegalovirus
Bacteria
V.cholerae O1
Vibrio O139
Non-O1 Vibrios
Vibrio parahemolyticus
Aeromonas
ETEC
EPEC
EaggEC
EIEC
EHEC (STEC)
Shigella spp.
Salmonella spp.
Campylobacter spp.
Yersinia enterocolitica
Clostridium difficile
Plesiomonas shigelloides
Protozoa
Giardia intestinalis
Cryptosporidium parvum
Microsporidia
Isospora belli
Cyclospora cayetanensis
Entamoeba histolytica
Balantidium coli
Helminths
Strongyloides stercoralis
Schistosoma spp.
Watery
diarrhea
Bloody
diarrhea
+
+
+
+
+
–
–
–
–
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
–
–
–
+
–
–
–
–
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
–
–
–
–
–
+
+
–
–
–
+
ETEC, enterotoxigenic Escherichia coli; EPEC, enteropathogenic E. coli; EAggEC, enteroaggregative E. coli; EIEC,
enteroinvasive E. coli; EHEC, enterohaemorrhagic E. coli.
Bloody diarrhea is the clinical presentation of severe
bacterial colitis, which is caused by invasive enteric
pathogens, for example Shigella spp., Salmonella spp.,
Campylobacter jejuni, Yersinia enterocolitica, enteroinvasive E. coli, enterohemorrhagic E. coli, Entamoeba histolytica and Balantidium coli. Some cases of Vibrio
parahemolyticus, Aeromona spp., and Plesiomona spp.
may also present as bloody diarrhea, especially later in
the course of acute diarrhea (see Table 3).
Bloody diarrhea
Diarrhoea where the stool on macroscopic observation
contains blood mixed up with feces or inseparable from
the stool is classified as bloody diarrhea. Microscopically, the feces generally contain numerous red blood
cells and white blood cells.
Clinical dehydration
For the purpose of this guideline, the term ‘clinical
dehydration’ refers to moderate and/or severe dehydra-
S58
S Manatsathit et al.
tion, and does not include mild diarrhea or mild
dehydration.
All cases of acute diarrhea would have dehydration
due to loss of fluid and electrolytes. Even mild diarrhea
would have some degree of dehydration, but this may
be difficult to assess quantitatively. Adults normally
have better compensatory mechanisms than children
through the larger body fluid reserve, the better kidney
compensatory mechanisms, and better response to
correct thirst. Together with poorer tissue elasticity
and slower shift of extra cellular fluid, the clinical
signs of dehydration in adults would be less obvious
than in children. Severity of dehydration does not
always correlate with severity of diarrhea. Some may
rely on the subjective symptoms alone to classify
severity of diarrhea while it is more reliable to evaluate
the severity of dehydration from objective signs. The
proper assessment of severity of dehydration should
utilize both subjective and objective evidence (see
Table 4).
Watery diarrhea with clinical dehydration
In general, severe watery diarrhea with severe dehydration is mostly caused by V. cholerae serogroup O1. There
are also other organisms that cause a similar clinical
picture as cholera. They are Vibrio O139,16 otherNon-O1 vibios17 and sometimes Vibrio parahemolyticus,
Aeromonas spp.18 and diarrheagenic E. Coli.19,20
Although diarrhea caused by these organisms is often
milder than cholera, more severe cases may occur,
which should be treated in the same fashion as severe
watery diarrhea. On the other hand, it should be noted
that during epidemics, or even in an endemic area for
cholera, patients with cholera may be found to have only
mild diarrhea, and they should be managed differently
from the suggested algorithm (see Appendix).
Although severe profuse watery diarrhea alone is
highly suggestive of cholera, it should be stressed that
Table 4
other features are also important, for example the very
abrupt onset of acute diarrhea that occurs in a matter
of hours, the rapid progression to profound dehydration, the absence of fever and abdominal pain, and the
presence of muscle cramps.16,21,22 In the obvious cases,
stools are often greenish-yellow clear watery with very
little food residue. Signs of dehydration should be
present and sometimes are very prominent. Dark field
microscopy (DFM) and stool culture should be done
in all cases. Stool examination with fine microscopic
adjustment could also reveal shooting bacteria, but
there are no red blood cells or white blood cells. In
nonendemic areas, once DFM or stool culture is positive for cholera, notification of the area health authority should be done as soon as possible.
It should be noted that in endemic areas, during outbreaks or seasonal epidemics of cholera, watery diarrhea
of all severity should be treated as cholera and stool
culture should be done to confirm in all cases (see
Appendix).
Treatment: The treatment of watery diarrhea should
focus mainly on fluid and electrolyte replacement. In
patients with mild dehydration, and with little or no
vomiting, oral rehydration therapy using oral rehydration salts solution (ORS) should be administered at
approximately 1.5 times the volume of stool loss in
24 h without discontinuing dietary intake.23 In moderate to severe dehydration, prompt aggressive intravenous fluid repletion and supportive care can obviate
the high mortality that is associated with the disease.
Also if vomiting is severe and the deficit cannot be
replaced solely by ORS, intravenous fluids in the form
of Ringer lactate will be required. In moderate to severe
diarrhea, at least half of the calculated deficit should be
replaced within 4 h and the rest is to be replaced within
24 h.24 Evaluation of fluid and electrolyte deficit is
crucial in calculating the amount of fluids to replace.
Hence, stool volume loss should be closely monitored
Classification of severity of dehydration
Mild
Subjective
General state
Ability to perform daily
activities
Thirst
Objective signs
Pulse
Blood pressure
Postural hypotension
Jugular venous pressure
Dry mucosa (mouth, tongue)
Skin turgor
Sunken eye balls
Alert, active, up and about
Able to perform daily
activities without difficulty
Not increased
Normal
Normal
No
Normal
No
Good
No
Moderate
Weak, lethargic.
Able to sit and walk
Able to perform daily
activities with some
difficulty, e.g. stays away
from work, needs support
Increased thirst
Tachycardia
Normal or decrease
10–20 mmHg systolic
Yes or no
Normal or slightly flat
Slight
Fair
Minimal
Severe
Dull, inactive.
Unable to sit or walk
Unable to perform daily
activities, stays in bed or
needs hospitalization
Feels very thirsty
Tachycardia
Decrease > 20 mmHg systolic
Yes
Flat
Severe
Poor
Sunken
Acute diarrhea in adults
and, if possible, weighed or accurately measured. In
those patients who are not sick enough and still can go
to toilets on their own, it may be difficult to estimate
accurately the amount of deficit and ongoing loss.
Where culturally acceptable the use of ‘cholera cots’ can
be very helpful to monitor the amount of ongoing loss.
If cholera cots are not available, it may be safer to
replace twice the amount of estimated loss and closely
monitor the status of hydration of the patient.
Antibiotics, when given to cholera patients, reduce
stool volume loss and shorten the clinical course.25 If
there is recent epidemiological data available, the
empiric antibiotics should be given according to the
sensitivity of Vibrio cholerae in the region. In cases where
antibiogram is not available, tetracycline 2 g daily for
3 days should be the treatment. Alternatively, doxycycline 300 mg as a single oral dose, or 100 mg twice
daily for 3 days, and ciprofloxacin 500 mg twice daily
for 3 days (especially in regions where resistance
to tetracycline is greater than 20%), have all been
recommended. For pregnant women, furazolidone
400 mg/day for 3 days has been suggested. Antidiarrheal
drugs may be somewhat effective in reducing enteric
symptoms, but they play a minor role in the treatment
of watery diarrhea and cannot be routinely recommended. (Loperamide is not indicated for patients with
severe watery diarrhea, for example cholera, but for
watery diarrhea in travelers, loperamide can be very
helpful). Treatment should rely only on rehydration
therapy and antibiotics only. Recently the use of resistant starch has been shown to be of benefit in reducing
stool volume loss and shortening the clinical course in
adult patients with cholera.26
Watery diarrhea without dehydration
Patients in this group comprise the majority of cases of
acute diarrhea in adults. They are often mild and are
not accompanied with signs of dehydration.They represent acute gastroenteritis that are usually caused by
enteric pathogens which have a self-limited course
and generally does not need antibiotics (except in
patients with extreme ages), for example Non-O1
vibrios, Vibrio parahemolyticus, Aeromonas spp., Plesiomonas spp., Edwardsiella spp., Salmonella spp. It may
also include the milder and uncomplicated forms of
diarrhea from Vibrio cholerae, Vibrio O139, Shigella
boydii, Shigella sonnei, Campylobacter spp., Yersinia spp.,
and all groups of Escherichia coli.
In general, diarrhea is characterized by the passage of
loose or loose watery stools with some food residue in
the feces. These patients normally pass 4–8 stools a day
without or with minimal signs of dehydration. There
should be no gross blood or bloody mucoid material in
the stool. Fever could be present but is often mild and
does not last longer than two days. Abdominal pain and
vomiting may be severe in the first few days but gradually subsides in the following days. Abdominal tenderness should be absent, both to light and deep palpation.
If stool microscopic examination is available, it characteristically shows no ova or parasites, RBC or WBC.
However, small numbers of RBC and WBC are sometimes present microscopically, but do not exceed 20
S59
cells/HPF.27 These cases usually are not accompanied
with fever.
Treatment: As dehydration is often mild, the need for
fluid and electrolytes replacement may be less pressing
than in the group with clinical dehydration. Nevertheless, rehydration remains the mainstay of treatment in
this group of patients. As the disease is dynamic and
mild dehydration may progress to more severe dehydration, early hydration with oral rehydration therapy
(ORT) should be encouraged to prevent fluid deficits.
Intravenous fluid replacement is often not needed.
Administration of antibiotics is unnecessary and not
recommended. Antidiarrheals can be allowed and loperamide has been recommended for use as selfmedication in adults with mild acute diarrhea.28 (A brief
review of scientific information regarding efficacy, sideeffects and precautions for the use of these antidiarrheals follows.)
Particular attention should be paid to geriatric
patients over the age of 65 years, immunocompromised
patients, and patients with conditions predisposing to
septicemia. Patients in these categories will need antibiotics, usually orally administered but sometimes systemically (see Appendix).
Bloody diarrhea
Most acute bloody diarrhea is caused by Shigella spp.
and Campylobacter jejuni. Shigella dysenteriae and Shigella
flexneri, often produce a more severe disease with high
fever, while Shigella boydii and Shigella sonnei usually
cause a milder disease. Other enteric pathogens producing bloody diarrhea include Salmonella enteritidis,
Yersinia enterocolitica, Clostridium difficile, EHEC and
EIEC. Sometimes Aeromonas hydrophila and Plesiomonas shigelloides that have severe enough diarrhea
may also produce bloody diarrhea.29 Entamoeba histolytica infections commonly present as chronic diarrhea, but they may sometimes present as acute bloody
diarrhea with or without fever.
Bloody diarrhea is often accompanied by fever that
may persist for longer than 2 days and may be higher
than 38.5°C. Initially, these patients may pass watery
stools that rapidly progresses to bloody diarrhea and
dysentery. Dysentery is characterized by the frequent
passage (usually 10–30 times a day) of small-volume
stools consisting of blood, mucus and pus; this diarrhea
is accompanied by abdominal cramps and tenesmus,
the painful straining at stool that may lead to rectal
prolapse. Diagnosis is enhanced if microscopically RBC
and WBC are found in the stool.27,30 It is essential to
exclude amoebic colitis by examining fresh stool for
trophozoites. Seizures are rare in adults with bloody
diarrhea. Mild dehydration is common and severe dehydration is very rare. The hemolytic uremic syndrome
rarely complicates bloody diarrhea. Bacteremia is associated with higher-than-usual mortality and is more
common among elderly patients31–33 (see Appendix).
S60
Treatment: The mild dehydration in bloody diarrhea
can be readily corrected with ORT and intravenous
therapy is often not needed. The use of antibiotics in
most patients with bloody diarrhea reduces the duration of illness and can shorten the carrier stage. For
practical purpose, after having excluded amoebic colitis
and EHEC or STEC by careful stool examination, it is
acceptable to start empiric therapy with antibiotics
rather than waiting for stool culture results. If the local
antibiogram of Shigella spp. is known, the preferred
antibiotics can be selected. But if no information is
available, one of the fluoroquinolones is preferred. Norfloxacin 800 mg/day, ciprofloxacin 1000 mg/day or levofloxacin 500 mg/day for 3–5 days should be adequate
for healthy adults. For geriatric patients, or septicemic
prone conditions, ofloxacin or ciprofloxacin is preferred. It is imperative not to administer antimotility
agents, such as loperamide, diphenoxylate, atropine and
codeine, as the drugs are suspected of enhancing the
severity of disease by delaying excretion of organisms
and thus facilitating further invasion of the mucosa.
Stool examination
Although fresh stool examination under light
microscopy should be encouraged in every case,34 it
may not always be practicable or possible. In real life
situations, assessment of patients with acute diarrhea
may have to rely solely on history and physical examination. Hence, in the algorithm, stool examination is
recommended in patients with watery diarrhea with
dehydration and in patients with bloody diarrhea, but
not considered as essential in patients with watery diarrhea without dehydration. Depending on the availability, feasibility and local practice, stool examination
may be done early in some cases and when it is done,
the detection of microscopic RBC and WBC > 20
cells/HPF by early stool examination may have some
predictive value in detecting early cases of bloody
diarrhea. In patients with gross bloody diarrhea, stool
examination can provide essential information for
differentiating shigellosis from amebiasis.35 In addition,
dark-field microscopy (DFM) is strongly recommended
in all patients with watery diarrhea with dehydration.36,37 A positive DFM for shooting bacteria should
indicate the high possibility of Vibrio spp., especially
Vibrio cholerae, and appropriate antibiotics to eradicate
Vibrio cholerae should be promptly initiated. In situations in which DFM is not available, fine adjustment of
light microscopic examination to look for active motile
‘shooting’ bacteria can be a helpful alternative to diagnose Vibrio spp. as a cause of diarrhea. Presence of stool
ova and parasites in the stool should lead to appropriate therapy.
Stool culture
In general, stool culture is probably not necessary in
patients who present to physicians with mild diarrhea
without obvious signs of dehydration, and within the
first few days of onset of illness. In most such individ-
S Manatsathit et al.
uals, the diarrhea will probably subside before the
culture results become available.38,39 Stool culture is
advisable in patients with bloody diarrhea, moderate to
severe diarrhea with objective evidence of dehydration,
and those with diarrhea that does not subside after a
few days.40 In the situation of an outbreak, nosocomial
diarrhea, or the specific conditions of acute diarrhea
listed in Table 2, extensive work up with stool culture
should be encouraged (see Appendix).
‘Routine’ culture techniques vary from country to
country and hospital to hospital, depending on the
availability, feasibility and local practice. When diarrhea
is non-specific or indeterminate and there are limitations of resources and facilities, routine stool culture
with MacConkey agar is the minimal requirement.
Because most laboratories in the USA do not culture
routinely for Vibrio cholerae or other Vibrio spp., clinicians should request appropriate cultures for clinically
suspected cases.When cholera is suspected from a positive DFM or presence of shooting bacteria from
light microscopy, thiosulfate-citrate-bile-salt-sucrose
(TCBS) agar should be added to the routine MacConkey agar to detect Vibrio group organisms. Further
identification for Vibrio cholerae serotype and
serogrouping should be done, together with the identifications of Vibrio O139, Non-O1 Vibrio cholerae
and Vibrio parahemolyticus. When bloody diarrhea is
suspected, selective media for Shigella, for example
salmonella-shigella agar or XLD agar should be added
to the routine MacConkey agar. Micro-aerophilic cultivation technique with inhibitory media to detect
Campylobacter and special media for Yersinia should be
added to the routine culture.41,42 If traveler’s diarrhea is
diagnosed, culture for all bacterial causes should be performed. For suspected EHEC associated diarrhea, Sorbitol-MacConkey agar should be added to the routine
culture.43 For antibiotic-associated enterocolitis, detection of C difficile Toxin A and B using ELISA or tissue
culture assay should be done (see Appendix).
Fresh stool specimens should always be used when
possible to ensure that fastidious organisms that decompose easily are detected before they degenerate. Stool
specimens should be transported to the microbiology
department ideally within 2 h after the passage, but
8–12 h would also be acceptable.44 In cases in which
stool specimens are not available, rectal swabs should
be obtained and put in transport media until culture.
Unresolved diarrhea
All patients who do not improve after rehydration, with
or without antidiarrheals and/or empiric antibiotics,
should require re-evaluation after 3–5 days, depending
on the severity of the continuing illness. Such patients
should be informed to bring along his or her ‘fresh’ stool
specimen for microscopic re-examination and/or reculture at their next visit. They should be advised to
observe their stool. They should also be advised to
consult their physician for re-evaluation if the stool
character changes and becomes more watery or bloody,
if they develop high fever (> 38.5°C), if their stage of
Acute diarrhea in adults
S61
clinical dehydration does not improve, or if their
abdominal pain becomes more intense or persistent.
When the patient comes for the second visit, stool
examination and culture should be done especially if
they were not performed in the first visit. In cases of
bloody diarrhea without an identifiable pathogen, which
do not improve after empiric treatment, further
investigation by doing sigmoidoscopy or colonoscopy
together with biopsy is usually necessary.
Sigmoidoscopy/colonoscopy
Patients who were managed along the scheme of the
algorithm or have bloody diarrhea in spite of empiric
antibiotics, and did not improve, should be further
investigated by sigmoidoscopy or colonoscopy. Colonic
biopsy together with culture should be performed even
though the mucosa may look normal endoscopically.45
as possible. Selection of antibiotics for corresponding
enteropathogens should follow the antibacterial sensitivity of the pathogen that was isolated. In situations
where an antibiogram is not available, antibiotics selection should follow the available local or regional data
regarding antibiotic susceptibility in that region or
country. If no such information is available, the use of
conventional recommended antibiotics (as shown in
Table 5) is recommended. It must be noted that antibiotics are not recommended for some enteropathogens, as there is no information to confirm the
efficacy of antibiotic use or the available information
suggests that antibiotic use in this particular situation
may actually be deleterious. Again, it should be stressed
that dehydration needs to be properly corrected in all
cases, no matter the result of the stool culture.
Oral rehydration
Selective antibiotics for known pathogens
Whenever stool examination and culture results are
available, treatment should be as selective and specific
Table 5
In this article, the term ORS (Oral Rehydration Salts
Solution) and ORT (Oral Rehydration Therapy) are
used.To avoid confusion, clarification of these terms are
presented below.
Recommended antibiotics against specific enteric pathogens
Organism
Suggested antibiotics
Vibrio cholera O1
Tetracycline, 500 mg q.i.d. ¥ 3 d
Vibrio O139
Tetracycline, 500 mg q.i.d. ¥ 3 d
Other non-O1
Vibrio spp.46
Antibiotics are usually not required, except in
certain situations.a
Tetracycline, 500 mg q.i.d. ¥ 3 d
Antibiotics are usually not required, except in
certain situations.b
Tetracycline, 500 mg q.i.d. ¥ 3 d
Vibrio parahemolyticus47
Shigella species
Fluoroquinolone* ¥ 3 d
Non-typhoidal species
of Salmonella
Antibiotics are usually not required, except in
certain situations.c
Fluoroquinolone* ¥ 5–7 d
Antibiotics are usually not required, except in
certain situations.a
Fluoroquinolone* ¥ 3 d
Antibiotics are usually not required, except in
certain situations.d
Fluoroquinolone* ¥ 3 d
Antibiotics are usually not required, but may be
required in certain situations.e
Fluoroquinolone* ¥ 3 d
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
Aeromonas species
Plesiomonas species
Enterotoxigenic
Escherichia coli
Alternative antibiotics
Doxycycline, 300 mg single dose
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
Fluoroquinolone* ¥ 3 d
Doxycycline, 300 mg single dose
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
Fluoroquinolone* ¥ 3 d
Doxycycline, 300 mg single dose,
Fluoroquinolone* ¥ 3 d
Ceftazidime# 1 g q 6 h ¥ 5–7 d
Doxycycline, 300 mg single dose
Fluoroquinolone* ¥ 3 d
Gentamicin#, 80 mg ¥ 5–7 d
Cefotaxime#, 1 g q.i.d. ¥ 5–7 d
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
Nalidixic acid 1 g/day ¥ 5 d
Ceftriaxone#, 1 g b.i.d. ¥ 5–7 d
Azithromycin 250 mg single dose
TMP-SMZ, 160–800 mg b.i.d. ¥ 5–7 d
(if susceptible)
Ceftriaxone#, 1 g b.i.d. ¥ 7–14 d
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
(if susceptible)
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
(if susceptible)
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
(if susceptible)
S62
Table 5
S Manatsathit et al.
(continued)
Organism
Enteropathogenic
Escherichia coli
Enteroinvasive
Escherichia coli
Enteroaggregative
Escherichia coli48
Enterohaemorrhagic
Escherichia coli
(STEC)
Campylobacter species
Yersinia species
Toxigenic Clostridium
difficile
Suggested antibiotics
Alternative antibiotics
Antibiotics have no established therapeutic
value and are usually not required, except in
certain situations.e
Antibiograms are needed. (Mostly in children)
Antibiotics are usually not required, except in
certain situations.e
Fluoroquinolone* ¥ 3 d
Fluoroquinolone* ¥ 3 d
Role of antibiotics is unclear and administration
should be avoided as they may be harmful.
(may predispose to hemolytic uremic
syndrome
Antibiotics are usually not required, except in
certain situations.f
Erythromycin 500 mg b.i.d. ¥ 5 d
Antibiotics are usually not required, except in
certain situations.g
Fluoroquinolone* ¥ 3 d
Offending antibiotics should be withdrawn if
possible.
Metronidazole, 250–500 mg q.i.d. ¥ 10–14 d
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
(if susceptible)
TMP-SMZ, 160–800 mg b.i.d. ¥ 3 d
(if susceptible)
Fluoroquinolone* ¥ 5 d
Combination of doxycycline and
aminoglycoside, or TMP-SMZ, or
fluoroquinolone
Vancomycin 125–250 mg q.i.d. ¥ 10-14 d
a
antibiotics may be required in septicemic prone conditions e.g. cirrhosis, or immunocompromised hosts
antibiotics may be required in severely ill patients, or traveler’s diarrhea, or septicemic prone conditions e.g. cirrhosis, uncontrolled diabetes mellitus, or immunocompromised hosts
c
antibiotics may be required in severely ill patients, or age < 6 months or > 65 year old, or immunocompromised hosts, or septicemic prone conditions e.g. patients with prosthesis, valvular heart disease, or severe atherosclerosis, or malignancy, or uremia,
or uncontrolled diabetes mellitus.
d
antibiotics may be required in severely ill patients, or immunocompromised hosts
e
antibiotics may be required in severely ill patients, traveler’s diarrhea, or immunocompromised hosts, or septicemic prone
conditions, or uncontrolled diabetes mellitus.
f
antibiotics may be required in severely ill patients, traveler’s diarrhea
g
antibiotics may be required in severely ill patients, or associated bacteremia, or when bacteremia is suspected, or immunocompromised hosts,
*fluoroquinolone, for example 300 mg ofloxacin, 400 mg norfloxacin, or 500 mg ciprofloxacin b.i.d.
#
antibiotics for suspected septicemic cases
b
Oral rehydration salts solution (ORS)
Oral rehydration salts solution refers to the oral rehydration salts formula that is recommended by WHO. It
contains sodium chloride 3.5 g, sucrose 40 g (or glucose
20 g), trisodium citrate dihydrate 2.9 g (or sodium
bicarbonate 2.5 g) and potassium chloride 1.5 g in one
litre of clean drinking water. This combination should
give the concentration of sodium 90 mEq/L, potassium
20 mEq/L, chloride 80 mEq/L, HCO3 30 mEq/L and
glucose 111 mmol/L.49
Oral rehydration therapy (ORT)
Oral rehydration therapy in the context of these guidelines refers to the use of informal oral rehydration
formulas or electrolyte packages with lower sodium
concentration than the one recommended by WHO. It
also refers to non-ORS measures of rehydration, including various natural or formulated electrolyte containing
drinks.50
Adult patients with watery diarrhea and clinical dehydration should receive the proper WHO-recommended
ORS formula to correct their dehydration, especially in
endemic areas of cholera. In other parts of the world
where cholera is not a problem, a milder formula may
be accepted. Patients with mild dehydration or patients
with all types of diarrhea without obvious evidence
of clinical dehydration can also use the WHO ORS
formula in conjunction with intermittent free water
drinking. In adults, the chance of having hyponatremia
or hypernatremia may be much greater in the elderly.31
Hence, ORT or usage of lower sodium concentration of
ORS, may be more appropriate in elderly patients. In
geriatric patients, periodic assessment of serum electrolytes may be necessary. The super ORS, which
Acute diarrhea in adults
contain glycine or starch (cereal-based formulations)
are receiving increased attention.51 Because of their
lower osmolarity, they may reduce stool output and
better enhance electrolytes absorption. The use of resistant starch to provide colonic short chain fatty acids
may also be of importance.51
In general, ORS or ORT should be taken by mouth
slowly and intermittently by ‘sipping’ little by little, not
‘drinking’ in large amount in a short period of time.The
amount to be taken should be approximately 1.5–2
times the estimated amount of deficit plus concurrent
loss.
Intravenous fluid replacement
For initial management of severely dehydrated or hypovolemic shock patients, immediate intravenous fluid
replacement is essential. Patients with moderate or
milder degree of dehydration may also need intravenous
fluid replacement if they have severe vomiting and are
unable to drink ORS properly. Patients with dull consciousness, who may harbor the risk of aspiration,
should also be rehydrated intravenously. Ringer’s lactate
is best recommended for all forms of acute diarrhea in
adults, as it contains potassium 4 mEq/L, which can
be replaced rapidly in large amounts according to the
severity of deficit. The total fluid deficit in severely
dehydrated patients can be replaced safely within the
first 4 h of therapy, half within the first hour.52 The
volume of fluid to be administered is determined by the
rate of stool losses and the degree of pre-existing dehydration. Meanwhile, oral therapy usually can be initiated with the goal of maintaining fluid intake equal to
the ongoing loss. However, patients with continued
large-volume diarrhea might require prolonged intravenous treatment to keep up with gastrointestinal fluid
losses. It should also be used with additional potassium
supplements by mouth. The oral route of rehydration
and potassium replacement is safer than the intravenous
route and is physiologically regulated by thirst and urine
output.
S63
oping world, where diarrhea is very prominent. In
industrialized countries, the antidiarrheal compounds
may be cost effective and useful in returning people
more quickly to work and school during a bout of
diarrhea.
There is a wide variety of antidiarrheal drugs available on the market. Physicians in each region of the
world will have to keep in mind the cost-risk-benefit
ratios and make their own judgment in selecting or
recommending the antidiarrheals. In the following
paragraphs the evidence supporting the use of each
antidiarrheal drug is briefly reviewed, so that physicians
can decide which to use by judging from their efficacy,
side-effects, indications and contra-indications based
on the available literature. Antidiarrheal drugs are
grouped and discussed under the following topics.
Antiperistaltics or antimotility drugs
Most available antiperistalic agents act by altering
intestinal motility. Some also may have mild proabsorptive or antisecretory activity. They include
loperamide, diphenoxylate, codeine, tincture opium and
other opiates.They may be helpful in secretory diarrhea
of mild to moderate severity by reducing the frequency
and volume of stools.53–55 Among all antimotility drugs,
loperamide is the most commonly recommended agent
for use in uncomplicated diarrhea.28,56 However, such
antimotility agents are contraindicated in diarrhea
caused by invasive pathogens because the induced
intestinal stasis may enhance tissue invasion by the
organisms or delay their clearance from the bowel.
Hence, bloody diarrhea with high fever, immunocompromised host and septicemic prone conditions with
diarrhea should not be given this group of drugs.
Some of these drugs may cause addiction, if they are
to be administered for a long period. Suppression of respiration is significant in children and may be harmful
in elderly people with chronic lung disease. The newer
loperamide preparation, loperamide oxide, may be the
drug in this group with the least side-effects.57 Response
to loperamide can vary from one person to another.The
aim should be to reduce the frequency of diarrhea, not
to ‘stop’ diarrhea.
Antidiarrheal drugs
While every effort should be made to identify and
correct the specific causes of diarrhea, in many cases,
causes that are specific and potentially treatable are
often not identifiable. Identification is not possible and
symptomatic therapy alone is commonly indicated.
Although most diarrheas are self-limited, some
antidiarrheal drugs may help in reducing amount of
fluid loss, frequency and consistency of stool, or shorten
the clinical course of diarrhea. The addition of antidiarrheal drugs improves the quality of life to a certain
extent at the financial cost of the drugs.The cost-benefit
ratio of using various antidiarrheal agents has not
been properly studied. As acute diarrhea is a very
common condition affecting large numbers of people,
the routine usage of antidiarrheals could mean a great
financial burden to countries, especially in the devel-
Anticholinergics
They include atropine, hyoscine, hyoscyamine and dicyclomine. They are not effective in reducing the frequency and volume of stools, but may have some value
in selected cases in reducing pain from abdominal
cramps.58 High dose of anticholinergics may cause dry
mouth, urinary retention, blurred vision, palpitation,
ileus and exacerbation of glaucoma.
Adsorbents
There are a variety of drugs in this group, for example
activated charcoal, kaolin, pectin, dioctahedral smectite,
attapulgite (anhydrous aluminum silicate), aluminum
hydroxide and tannic acid. Theoretically these medications adsorb toxins produced by toxigenic bacteria and
S64
act by preventing their adherence to intestinal membranes. To be effective, they have to be given very early
before the toxins are fixed to intestinal mucosa. Their
efficacy depends on their potency to adsorb toxins,
some preparations, for example dioctahedral smectite,
attapulgite and bismuth preparations are more effective
in adsorbing toxins than others.59–61 In clinical trials,
they can increase stool consistency and decrease stool
frequency, but cannot reduce the amount of fluid loss.
They only mask its extent and dehydration is not prevented.When prescribing these medications, it is important to maintain adequate hydration and proper diet,
especially in the elderly. Adsorbents are not effective in
patients with febrile bloody diarrhea. In rare instances,
they may cause constipation. Prolonged use may interfere with some medications, for example theophylline
and digoxin. Psyllium and other hydrophilic agents are
bulk forming agents, which absorb water and thereby
enhance stool consistency. Commonly, they are used in
chronic diarrhea and irritable bowel syndrome, not in
acute diarrhea.
Probiotics
Probiotics are non-pathogenic organisms, for example
Lactobacillus acidophilus and Saccharomyces boulardii,
which multiply in the patient’s intestine and produce
metabolites, which increase acidity of stool and prohibit
the growth of enteropathogens. They prevent the invasion of bacteria in intestine tissue, and produce short
chain fatty acids that are beneficial for intestine recovery, and increase the rate of fluid and electrolyte absorption. In children, there are studies which show that the
use of probiotics could reduce the clinical course of
acute diarrhea.62–64 In adults, they are used mainly in
chronic diarrhea and relapse of antibiotic associated
enterocolitis.65
S Manatsathit et al.
controlling motility and secretion of the gut. As 5HT
is also a neurotransmitter found in the brain and
the enteric nervous system (ENS). The antagonists of
5HT3 receptor were found to inhibit extrinsic sensory
neuron stimulation (which can inhibit nausea, vomiting, stomach pain and bloating) and reduce peristalsis
and secretory reflex. As a result, they help to reduce
stool volume and improve stool consistency. Another
newer antisecretory agent is oral enkephalinase
inhibitor (Racecadotril). It prevents the degradation of
endogenous opioids (enkephalins), thereby reducing
hypersecretion of water and electrolytes into the intestinal lumen. Clinical trials that show the efficacy of these
drugs in the management of acute diarrhea in children
and adults are being validated.73,74 Octreotide, which is
a long-acting synthetic analog of somatostatin, has a significant antisecretory effect.75 It is expensive and has to
be administered subcutaneously. It is more reasonable
to prescribe in otherwise refractory cases of chronic
diarrhea.
Herbal medicine
There are an enormous numbers of herbal medicines
around the world that are claimed to be effective in
treating diarrhea. However, there is very little scientific
data to support or confirm the efficacy of these medicines, or if results are available, they are mostly inconclusive and anecdotal. However, they are cheap and
locally available. Administration of herbal medicine that
is shown to be harmless in mild watery diarrhea without
dehydration can be locally accepted, provided that the
dehydration is properly corrected and patients with
febrile dysentery are properly managed. Herbal medicines should not be recommended in severe diarrhea no
matter the causes.
Antisecretory drugs
CONCLUSION
There are many drugs in everyday use that have antisecretory effects in vitro, for example phenothiazine,
chlorpromazine, aspirin, indomethacin, lithium carbonate, and calmodulin-inhibitors. They work by a
variety of different mechanisms including inhibition of
prostaglandins and effects on cyclic AMP, calmodulin
inhibition,66 inhibition of gut hormones and encephalinase inhibition of chloride channels.67 But some of these
drugs have to be administered in very high doses to give
effective antisecretory effects in vivo. Hence, their drugrelated side-effects preclude them from being used
effectively.68,69 This group of drugs is more physiologic
in approach and may become the ideal agents for use
in acute diarrhea. Bismuth salts preparations, according
to their mode of action, are also an antisecretory agents.
They are found to be as effective as loperamide, and
reduce the number of stools passed by about 50%, with
improvement in other associated symptomatology.70,71
The untoward side-effects of bismuth preparations are
blackened stool, blackened tongue, tinnitus and fecal
impaction.72
Recently, drugs that affect 5-hydroxytryptamine
(5HT) or serotonin were found to have a pivotal role in
Acute diarrhea in adults is a common every-day condition all over the world. Besides acute infectious diarrhea, the definition also encompasses many intestinal
conditions that may present as acute diarrhea. Stool
examination and culture results are often not available,
and proper hydration together with empiric treatment
has to be initiated. A practical approach for the management of adult patients with acute diarrhea is presented in an algorithmic diagram. After careful history
taking and a physical examination to exclude other conditions that may present as acute diarrhea, and other
specific situations of acute diarrhea that deserve to be
approached differently, patients are classified as having
predominately diarrhea or predominately vomiting.The
diarrhea predominant group is further classified into
watery diarrhea and bloody diarrhea subgroups by their
gross stool appearance. The watery diarrhea subgroup
with clinical dehydration will have to exclude cholera by
stool examination with dark field microscopy confirmed
later by stool culture. The watery diarrhea without clinical dehydration subgroup is managed by ORT with or
without antidiarrheals.The bloody diarrhea subgroup is
Acute diarrhea in adults
treated with antibiotics either empirically or after stool
examination and culture to rule out EHEC or STEC.
If patients do not improve after the first visit and specific pathogens causing diarrhea are identified, specific
antibiotics should be administered according to the sensitivity results or data from the community. Further
investigation by repeating stool examination and culture
together with sigmoidoscopy or colonoscopy are essential if the patient does not get better. There are special
situations in acute diarrhea that require special considerations and these are discussed in detail.
REFERENCES
1 Stone DH, Mitchell S, Packham B,Williams J. Prevalence
and first-line treatment of diarrhoeal symptoms in the
community. Public Health 1994; 108: 61–8.
2 van Berkestijn LG, Kastein MR, Lodder A, de Melker
RA, Bartelink ML. How well are patients treated in
family practice? Quality of consultations for non-acute
abdominal complaints. Int. J. Qual. Health Care 1998; 10:
221–33.
3 World Health Organization. The World Health Report
1996: Fighting disease, fostering development. Geneva:
WHO, 1996.
4 Cohen ML. Epidemiology of diarrhoeal disease: infectious diarrhoea. Infect. Dis. Clin. North Am. 1988; 2:
557–70.
5 Feldman R., Banatvala N. The frequency of culturing
stools from adults with diarrhoea in Great Britain.
Epidemiol. Infect. 1994; 113: 41–4.
6 Gangarosa RE, Glass RI, Lew JF, Boring JR. Hospitalizations involving gastroenteritis in the United States,
1985 the special burden of the disease among the elderly.
Am. J. Epidemiol. 1992; 135: 281–90.
7 Thoren A, Lundberg O, Bergdahl U. Socioeconomic
effects of acute diarrhoea in adults. Scand. J. Infect. Dis.
1988; 20: 317–22.
8 CDC. Diagnosis and Management of Foodborne Illnesses. A Primer for Physicians. Morb. Mortal.Wkly Rep.
2001; 50: 1–70.
9 Ramakrishna BS, Kang G, Rajan DP, Mathan M, VIM.
Isolation of Vibrio cholerae O139 from the drinking water
supply during an epidemic of cholera. Trop. Med. Int.
Health 1996; 6: 854–8.
10 Reardon M, Coleman P, Twomey C, Hyland CM. Rectal
examination in hospital patients. Ir. Med. J. 1995; 88:
220–1.
11 Tauxe RV, Hughes JM. Foodborne disease. In: Mandel,
GF Bennett, JE Dohr, R. eds. Principles and Practices of
Infectious Diseases. 4th edn. New York: Churchill Livingstone, 1997; 1012.
12 Kapikian AZ, Estes MK, Chanock RM. Norwalk group
of viruses. In: Fields BN, Knipe DM, Howley PM,
eds. Fields Virology, 3th edn. Philadelphia, Pennsylvania:
Lippincott-Raven, 1996; 783–810.
13 Tallett S, MacKenzie C, Middleton P, Kerzner B, Hamilton R. Clinical, laboratory, and epidemiologic features of
a viral gastroenteritis in infants and children. Pediatrics
1977; 60: 217–22.
14 Blacklow NR, Greenberg HB, Engl N. Viral gastroenteritis. J. Med. 1991; 325: 252–61.
S65
15 Stenhoff MC, Douglas RGJ, Greenberg HB, Callahan
DR. Bismuth subsalicylate therapy of viral gastroenteritis. Gastroenterology 1980; 78: 1495–9.
16 Bhattacharya SK, Bhattacharya MK, Nair GB et al.
Clinical profile of acute diarrhoea cases infected with the
new epidemic strain of Vibrio cholerae O139: designation
of the disease as cholera. J. Infect. 1993; 27: 11–15.
17 Campos E, Bolanos H, Acuna MT et al. Vibrio mimicus
diarrhoea following ingestion of raw turtle eggs. Appl.
Environ. Microbiol. 1996; 62: 1141–4.
18 Alabi SA, Odugbemi T. Occurrence of Aeromonas
species and Plesiomonas shigelloides in patients with and
without diarrhoea in Lagos, Nigeria. J. Med. Microbiol.
1990; 32: 45–8.
19 Sack RB, Gorbach SL, Banwell JG, Jacobs B, Chatterjee
BD, Mitra RC. Enterotoxigenic Escherichia coli isolated
from patients with severe cholera-like disease. J. Infect.
Dis. 1971; 123: 378–85.
20 Sack DA, McLaughlin JC, Sack RB, Orskov F, Orskov I.
Enterotoxigenic Escherichia coli isolated from patients
at a hospital in Dacca. J. Infect. Dis. 1977; 135: 275–80.
21 Keen MF, Bujalski L. The diagnosis and treatment of
cholera. Nurse Pract. 1992; 17: 53–6.
22 Fukuda JM,Yi A, Chaparro L, Campos M, Chea E. Clinical characteristics and risk factors for Vibrio cholerae
infection in children. J. Pediatr. 1995; 126: 882–6.
23 Bojalil R., Guiscafre H, Espinosa P et al. A clinical training unit for diarrhoea and acute respiratory infections:
an intervention for primary health care physicians in
Mexico. Bull.World Health Organ. 1999; 77: 936–45.
24 Seas C, DuPont HL,Valdez. LM et al. Practical guideline
for treatment of cholera. Drugs 1996; 51: 966–73.
25 Mahalanabis D, Molla AM, Sack DA. Clinical management of cholera. In: Barua D, Greenough WB eds.
Cholera. New York: Plenum, 1992; 253.
26 Ramakrishna BS, Venkataraman S, Srinivasan P, Dash P,
Young G, Binder H. Amylase-resistant starch plus oral
rehydration solution for cholera. N. Engl. J. Med. 2000;
342: 308–13.
27 Alvarado T. Fecal leucocytes in patients with infectious
diarrhoea. Trans. R. Soc.Trop. Med. Hyg 1983; 77: 316–20.
28 Wingate D, Phillips SF, Lewis SJ et al. Guidelines for
adults on self-medication for the treatment of acute diarrhea. Aliment Pharmacol. Ther. 2001; 15: 773–82.
29 Kain KC, Kelly MT. Clinical features, epidemiology, and
treatment of Plesiomonas shigelloides diarrhea. J. Clin.
Microbiol. 1989; 27: 998–1001.
30 Siegel D, Cohen PT, Neighbor M et al. Predictive value
of stool examination in acute diarrhea. Arch. Pathol. Lab.
Med. 1987; 111: 715–8.
31 Bennett RG, Greenough WB. Approach to acute diarrhea
in the elderly. Gastroenterol. Clin. North Am. 1993; 22 (3):
517–33.
32 Lew JF, Glass RI, Gangarosa RE, Cohen IP, Bern C, Moe
CL. Diarrheal deaths in the United States, 1979 through
1987. A special problem for the elderly. JAMA 1991; 265:
3280–4.
33 Ramakrishna BS. Gastrointestinal infections in the
elderly. In: Sharma OP ed. Geriatrics and. Gerontology:
ANB Publishers. New Delhi, 1999; 186–95.
34 Thorne GM. Diagnosis of infectious diarrheal diseases:
infectious diarrhea. Infect. Dis. Clin. North Am. 1988; 2:
747–74.
S66
35 Speelman P, McGlaughlin R., Kabir I, Butler T. Differential clinical features and stool findings in shigellosis
and amoebic dysentery. Trans. Roy Soc. Trop Med. Hyg.
1987; 81: 549–51.
36 Benenson AS, Islam MR, Greenough WB. Rapid identification of Vibrio cholerae by darkfield microscopy. Bull.
WHO 1964; 30: 827–31.
37 Pryor WM, Bye WA, Curran DH, Grohmann GS. Acute
diarrhoea in adults: a prospective study. Med. J. Aust.
1987; 147: 490–3.
38 Koplan JP, Fineberg HV, Ferraro MJB, Rosenberg ML.
Value of stool cultures. Lancet 1980; 2: 413–6.
39 Roncoroni AJ, de Cortigianni MR, Garcia Damiano MC.
Cost and effectiveness of fecal culture in the etiologic
diagnosis of acute diarrhea. Bol. Oficina Sanit. Panama
1989; 107: 381–7.
40 Bauer TM, Lalvani A, Fahrenbach J et al. Derivation and
validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized adults. JAMA 2001; 285: 313–9.
41 Tabibian N, Clarridge JE, Smith JL, Alpert E, Shaw I,
Graham DY. Clinical impact of stool cultures for Campylobacter in adults with acute or chronic diarrhoea. South
Med. J. 1987; 80: 709–11.
42 Feeney GF, Kerlin P, Sampson JA. Clinical aspects of
infection with Yersinia enterocolitica in adults. Aust. NZ J.
Med. 1987; 17: 216–9.
43 Tarr PINM, Clausen CR, Watkins SL, Christie DL,
Hickman RO. Escherichia coli 0157. H7 and the hemolytic
uremic syndrome: importance of early cultures in establishing the etiology. J. Infect. Dis. 1990; 162: 553–6.
44 Lew JF, LeBaron CW, Glass RI et al. Recommendations
for collection of laboratory specimens associated with
outbreaks of gastroenteritis. Morb. Mortal. Wkly Rep.
1990; 39: 14.
45 Bellaiche G, Le Pennec MP, Slama JL et al. The value
of rectosigmoidoscopy and the bacteriologic culture of
colon biopsies in the etiologic diagnosis of acute diarrhoea of adults. A prospective study of 65 patients. Ann.
Gastroenterol. Hepatol. (Paris) 1996; 32: 11–17.
46 Safrin S, Morris JG, Adams M et al. Non-O1 Vibrio
cholerae bactermia. case report and review. Rev. Infect.
Dis. 1988; 10: 1012–17.
47 Hally RJ, Rubin RA, Fraimow HS et al. Fatal Vibrio parahemolyticus septicemia in a patient with cirrhosis. Dig.
Dis. Sci. 1995; 40: 1257–60.
48 Wanke CA, Gerrior J, Blais V, Mayer H, Acheson D. Successful treatment of diarrhoeal disease associated with
enteroaggregative Escherichia coli in adults infected with
human immunodeficiency virus. J. Infect. Dis. 1998; 178:
1369–72.
49 Centuori S, Mati L, Foto E, Gellili L, Tamburlini G.
Success and constraints in the implementation of WHO
guidelines for the management of diarrhoea in Albania.
Minerva Pediatrica 1998; 50: 57–61.
50 Bahl R., Bhandari N, Bhan MK. Reduced-osmolarity
oral rehydration salts solution multicentre trial: implications for national policy. Indian J. Pediatr. 1996; 63:
473–6.
51 Molla AM, Molla A, Nath SK, Khatun M. Food-based
oral rehydration salt solutions for acute childhood diarrhoea. Lancet 1989; 2: 429–31.
S Manatsathit et al.
52 Rahman O, Bennish ML, Alam AN et al. Rapid intravenous rehydration by means of a single polyelectrolyte
solution with or without dextrose. J. Pediatr. 1988; 113:
654–60.
53 Multicentre general practice comparison of loperamide
and diphenoxylate with atropine in the treatment of acute
diarrhoea in adults. Br. J. Clin. Pract. 1979; 33: 77–9.
54 Bergstrom T, Alestig K, Thoren K, Trollfors B. Symptomatic treatment of acute infectious diarrhoea: loperamide
versus placebo in a double-blind trial. J. Infect. 1986; 12:
35–8.
55 van Loon FP, Bennish ML, Speelman P, Butler C.
Double blind trial of loperamide for treating acute watery
diarrhoea in expatriates in Bangladesh. Gut 1989; 30:
492–5.
56 Hughes IW. First-line treatment in acute non-dysenteric
diarrhoea. clinical comparison of loperamide oxide,
loperamide and placebo. [UK Janssen Res. Group
General Practitioners]. Br. J. Clin. Pract. 1995; 49: 181–5.
57 Dettmer A. Loperamide oxide in the treatment of acute
diarrhoea in adults. Clin. Ther. 1994; 16: 972–80.
58 Reves R., Bass P, DuPont HL, Sullivan P, Mendiola J.
Failure to demonstrate effectiveness of an anticholinergic drug in the symptomatic treatment of acute travelers’
diarrhea. J. Clin. Gastroenterol. 1983; 5: 223–7.
59 Wakinson MA. A lack of therapeutic response to kaolin
in acute childhood diarrhoea treated with glucose
electrolyte solution. J. Trop. Pediatr. 1982; 28: 308.
60 Leber W. A new suspension form of smectite (Liquid
‘Diasorb’) for the treatment of acute diarrhoea: a
randomized comparative study. Pharmatherapeutica 1988;
5: 256–60.
61 Zaid MR, Hasan M, Khan AA. Attapulgite in the treatment of acute diarrhoea: a double-blind placebocontrolled study. J. Diarrhoeal Dis. Res. 1995; 13: 44–6.
62 Kaila M, Isolauri E, Saxellin M, Arvilommi H, Vesikari
T. Viable versus inactivated lactobacillus strain GG in
acute rotavirus. Arch. Dis. Child 1995; 72: 51–3.
63 Elmer GW, Surawicz CM, McFarland LV, Biotherapeutic agents. A neglected modality for the treatment and
prevention of selected intestinal and vaginal infections.
JAMA 1996; 275: 870–6.
64 Guandalini S, Pensabene L, Zikri MA et al. Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial.
J. Pediatr. Gastroenteol. Nutr. 2000; 30: 50–60.
65 McFarland LV, Surawicz CM, Greenberg RN et al.
Prevention of beta-lactam-associated diarrhea by
Saccharomyces boulardii compared with placebo. Am. J.
Gastroenterol. 1995; 90: 439–48.
66 Okhuysen PC, DuPont HL, Ericsson CD et al. Zaldaride
maleate (a new calmodulin antagonist) versus loperamide in the treatment of traveler’s diarrhoea: randomized, placebo-controlled trial. Clin. Infect. Dis. 1995;
21: 341–4.
67 Roge J, Baumer P, Berard H, Schwartz JC, Lecomte JM.
The enkephalinase inhibitor, acetorphan, in acute diarrhoea. A double- blind, controlled clinical trial versus
loperamide. Scand. J. Gastroenterol. 1993; 28: 352–4.
68 Castor B, Thoren A, Barkenius G. Failure of aspirin in
symptomatic treatment of acute diarrhoea. J. Diarrhoeal
Dis. Res. 1991; 9: 29–32.
Acute diarrhea in adults
69 Islam MR, Sack DA, Holmgren J, Bardhan PK, Rabbani
GH. The use of chlorpromazine in the treatment of
cholera and other severe acute watery diarrheal diseases.
Gastroenterology 1982; 82: 1335–40.
70 DuPont HL. Nonfluid therapy and selected chemoprophylaxis of acute diarrhoea. Am. J. Med. 1985; 78
(Suppl.): 81–90.
71 Johnson PC, Ericsson CD, DuPont HL, Morgan DR,
Bitsura JA, Wood LV. Comparison of loperamide with
bismuth subsalicylate for the treatment of acute travelers’ diarrhoea. JAMA 1986; 255: 757–60.
72 DuPont HL, Flores Sanchez J, Ericsson CD et al.
Comparative efficacy of loperamide hydrochloride and
bismuth subsalicylate in the management of acute diarrhoea. Am. J. Med. 1990; 88 (Suppl.): 15S–19S.
73 Hamza H, Ben Khalifa H, Baumer P, Berard H, Lecomte
JM. Racecadotril versus placebo in the treatment of acute
diarrhoea in adults. Aliment Pharmacol. Ther. 1999; 13
(Suppl. 6): 15–9.
74 Salazar-Lindo E, Santisteban-Ponce J, Chea-Woo E,
Gutierrez M. Racecadotril in the treatment of acute
watery diarrhea in children. N. Engl. J. Med. 2000; 343:
463–7.
75 Abbas Z, Moid I, Khan AH et al. Efficacy of octreotide
in diarrhoea due to Vibrio cholerae: a randomized, controlled trial. Ann. Trop. Med. Parasitol. 1996; 90: 507–13.
76 Pentland B, Pennington CR. Acute diarrhoea in the
elderly. Age Ageing 1980; 9: 90–2.
77 Alapati SV, Mihas AA. When to suspect ischemic colitis.
Why is this condition so often missed or misdiagnosed?
Postgrad. Med. 1999; 105: 177–87.
78 Stek M. Traveler’s diarrhoea in the Mediterranean basin.
Mil. Med. 1980; 145: 628–9.
79 Taylor DN, Houston R., Shlim DR, Bhaibulaya M,
Ungar BL, Echeverria P. Etiology of diarrhea among travelers and foreign residents in Nepal. JAMA 1988; 260:
1245–8.
80 Haberberger RL, Mikhail IA, Burans JP et al. Travelers’
diarrhea among United States military personnel during
joint American-Egyptian armed forces exercises in Cairo.
Egypt. Mil. Med. 1991; 156: 27–30.
81 Beller M, Schloss M. Self-reported illness among
travelers to the Russian Far East. Public Health Rep. 1993;
108: 645–9.
82 Ericsson C, DuPont HL. Travelers’ diarrhea: approaches
to prevention and treatment. CID 1993; 16: 616–26.
83 Larson SC. Traveler’s diarrhea. Emer. Med. Clin. North
Am. 1997; 15: 179–89.
84 Peltola H GS. Travelers’ diarrhea epidemiology and
clinical aspects. Hamilton, Ontario: BC Decker Inc,
1997.
85 Aronsson B, Mollby R, Nord CE. Antimicrobial agents
and Clostridium difficile in acute enteric disease:
epidemiological data from Sweden, 1980–82. J. Infect.
Dis. 1985; 151: 476–81.
86 Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli
0157. H7 and the hemolytic–uremic syndrome. N. Engl.
J. Med. 1995; 333: 364–8.
87 Carter AO, Borczyk AA, Carlson JA et al. A severe outbreak of Escherichia coli 0157: H7–associated hemorrhagic colitis in a nursing home. N. Engl. J Med. 1987;
317: 1496–500.
S67
88 Karmali MA, Petric M, LIMC et al. The association
between idiopathic hemolytic uremic syndrome and
infection by verotoxin-producing Escherichia coli. J. Infect.
Dis. 1985; 151: 775–82.
89 Bender JB, Hedberg CW, Besser JM, Boxrud DJ, MacDonald KL, Osterholm MT. Surveillance by molecular
subtype for Escherichia coli O157: H7 infections in Minnesota by molecular subtyping. N. Engl. J Med. 1997; 337:
388–94.
90 Su C, Brandt LJ. Escherichia coli O157: H7 infection in
humans. Ann. Intern. Med. 1995; 123: 698–714.
91 Bell BP, Goldoft M, Griffin. PM, et al. A multistate outbreak of Escherichia coli O157: H7-associated bloody
diarrhoea and hemolytic uremic syndrome from hamburgers. The Washington experience. JAMA 1994; 272:
1349–53.
92 Seigler RL, Milligan MK, Burningham TH et al.
Long-term outcome and prognostic indicators in the
hemolytic–uremic syndrome. J. Pediatr. 1991; 118:
195–200.
93 Fitzpatrick MM, Shah V, Trompeter RS, Dillon MJ,
Barratt TM. Long-term renal outcome of childhood
haemolytic uraemic syndrome. BMJ 1991; 303: 489–92.
94 Walterspiel JN, Ashkenazi S, Morrow AL et al. Effect of
subinhibitory concentrations of antibiotics on extracellular Shiga-like toxin I. Infection 1992; 20: 25–9.
95 McFarland LV. Epidemiology of infectious and iatrogenic
nosocomial diarrhoea in a cohort of general medicine
patients. Am. J. Infect. Control 1995; 23: 295–305.
96 Cunha BA. Nosocomial diarrhoea. Crit. Care Clin. 1998;
14: 329–38.
97 Mylotte JM, Graham R., Kahler L,Young L, Goodnough
S. Epidemiology of nosocomial infection and resistant
organisms in patients admitted for the first time to an
acute rehabilitation unit. Clin. Infect. Dis. 2000; 30:
425–32.
98 Cartmill TD, Shrimpton SB, Panigrahi H, Khanna V,
Brown R., Poxton IR. Nosocomial diarrhoea due to a
single strain of Clostridium difficile: a prolonged
outbreak in elderly patients. Age Ageing 1992; 21: 245–
9.
99 Centers for Disease Control and Prevention. Foodborne
outbreaks of enterotoxigenic Escherichia coli. Rhode Island
New Hampshire, 1993 [published erratum appears in
MMWR Morb. Mortal.Wkly Rep. 1994; 43: 127] MMWR
Morb. Mortal.Wkly Rep. 1994; 43: 81–9.
100 Daniels NA, Bergmire-Sweat DA, Schwab KJ et al. A
foodborne outbreak of gastroenteritis associated with
Norwalk-like viruses: first molecular traceback to deli
sandwiches contaminated during preparation. J. Infect.
Dis. 2000; 181: 1467–70.
101 Gupta DN, Sen D, Saha MR et al. Report of an outbreak
of diarrhoeal disease caused by cholera followed by
rotavirus in Manipur. Indian J. Public Health 1990; 34:
62–5.
102 Hedberg CW, Levine WC, White KE et al. An international foodborne outbreak of shigellosis associated with
a commercial airline. JAMA 1992; 268: 3208–12.
103 Khuri-Bulos NAAK, Shehabi A, Shami K. Foodhandlerassociated Salmonella outbreak in a University hospital
despite routine surveillance cultures of kitchen employees. Infect. Control Hops. Epidemiol. 1994; 15: 311–4.
S68
104 Reves RRMA, Bartlett AV et al. Child day care increases
the risk of clinic vistis for acute diarrhoea and diarrhoea
due to rotavirus. Am. J. Epidemiol. 1993; 137: 97–107.
105 Bacillus cereus food poisoning associated with fried rice
at two child day care centers-Virginia 1993. MMWR
Morb. Mortal.Wkly Rep. 1994; 177–8.
106 Emont SL, Cote TR, Dwyer DM, Horan JM. Gastroenteritis outbreak in a Maryland nursing home. Md Med.
J. 1993; 42: 1099–103.
107 Sims RV, Hauser RJ, Adewale AO et al. Acute gastroenteritis in three community-based nursing homes. J.
Gerontol. Biol. Sci. Med. Sci. 1995; 50: M252–6.
108 Asplund S, Gramlich TL. Chronic mucosal changes of
the colon in graft-versus-host disease. Mod. Pathol. 1998;
11: 513–5.
109 van Kraaij MG, Dekker AW,Verdonck LF et al. Infectious
gastro-enteritis. an uncommon cause of diarrhoea in
adult allogeneic and autologous stem cell transplant
recipients. Bone Marrow Transplant 2000; 26: 299–
303.
110 Yeomans A, Davitt M, Peters CA, Pastuszek C, Cobb S.
Efficacy of chlorhexidine gluconate use in the prevention
of perirectal infections in patients with acute leukemia.
Oncol. Nurs. Forum 1991; 18: 1207–13.
111 Kraus A, Guerra-Bautista G, Alarcon-Segovia D. Salmonella arizona arthritis and septicemia associated with
rattlesnake ingestion by patients with connective tissue
diseases. A dangerous complication of folk medicine. J.
Rheumatol. 1991; 18: 1328–31.
112 Poulos JE, Cancio M, Conrad P, Nord HJ, Altus P. Non
0–1 Vibrio cholerae septicemia and culture negative neutrocytic ascites in a patient with chronic liver disease. J.
Fla. Med. Assoc. 1994; 81: 676–8.
113 Merlin M, Gandara S, Iannicillo H et al. Acute and
chronic diarrhoea in AIDS. Study 435 (HIV+) Patients,
Buenos Aires. Acta Gastroenterol. Latinoam 1996; 26:
15–22.
114 Weber R., Ledergerber B, Zbinden R. et al. Enteric infections and diarrhoea in human immunodeficiency virusinfected persons: prospective community-based cohort
study. Swiss HIV Cohort Study. Arch. Intern. Med. 1999;
159: 1473–80.
115 Du Pont HL, Marshall GD. HIV-associated diarrhea and
wasting. Lancet 1995; 346: 352–6.
116 Ramakrishna BS. Prevalence of intestinal pathogens in
HIV patients with diarrhea: implications for treatment.
Indian J. Pediatr. 1999; 66: 29–36.
117 Levine GI. Sexually transmitted parasitic diseases. Prim.
Care 1991; 18: 101–28.
118 Gagarin VV. Acute disorders of the mesenteric circulation among heart defect patients. Kardiologiia 1984; 24:
81–4.
119 Chan TY, Chow DP, Ng KC, Pang KW, McBride GA.
Vibrio vulnificus septicemia in a patient with liver
cirrhosis. Southeast Asian J.Trop Med. Public Health 1994;
25: 215–16.
120 Christenson B, Soler M, Nieves L, Souchet LM. Septicemia due to a non-0: 1, non-0: 139 Vibrio cholerae.
Bol. Asoc. Med. P. R. 1997; 89: 31–2.
121 Chan HL, Ho HC, Kuo TT. Cutaneous manifestations
of non-01 Vibrio cholerae septicemia with gastroenteritis
and meningitis. J. Am. Acad. Dermatol. 1994; 30: 626–
8.
S Manatsathit et al.
122 Bircks W, Reidemeister C, Sadony V, Schulte HD,Tarbiat
S. Diagnostic and therapeutic problems of septicemia
after valvular replacement. J. Cardiovasc Surg. (Torino)
1972; 13: 385–9.
123 Aksnes J, Abdelnoor M, Berge V, Fjeld NB. Risk factors
of septicemia and perioperative myocardial infarction in
a cohort of patients supported with intra-aortic balloon
pump (IABP) in the course of open heart surgery. Eur.
J. Cardiothorac Surg. 1993; 7: 153–7.
APPENDIX
The following specific conditions of acute diarrhea are
specifically mentioned here as there are theoretical basis
and scientific information to warrant special considerations. They should be managed differently from the
suggested algorithm in this report. These conditions
are:
Acute diarrhea in the elderly
Acute diarrhea that occurs in patients aged over 65
years is associated with higher mortality.31,32,76 Diarrhea
is a common problem among the elderly that can have
catastrophic results. Atherosclerosis predisposes older
adults to morbid sequelae from dehydration resulting
from diarrhea. Ischemic colitis is a serious differential
diagnosis especially in developed countries.77 Deaths
related to diarrheal illnesses are recognized among older
adults living in the community as well as among those
confined to nursing homes. Outbreaks have most often
been associated with excess deaths from diarrhea
among nursing-home patients. Although most cases of
dehydration from diarrhea result from gastrointestinal
infections, non-infectious causes of diarrhea related to
prescription of laxatives, side-effects of medications and
use of enteral feedings are common. Clostridium difficile
infection is particularly common among older adults in
hospitals and nursing homes, and relapsing disease in
these groups may be more frequent than among
younger adults. The approach to an elderly patient with
diarrhea is to ensure proper hydration using available
oral rehydration solutions, proceed with diagnostic tests
likely to yield a positive result, avoid the use of harmful
antiperistaltic drugs, and provide adequate follow-up of
the nutritional state. Antibiotics should be administered
in acute diarrhea due to invasive bacteria, especially
salmonella.
Traveler’s diarrhea
This is a specific entity that occurs after a person has
traveled from an industrialized country to a developing
country and experienced acute diarrhea. The risk
increases if the traveler consumes food from street
vendors rather than from a restaurant or a hotel. Symptoms and severity depend on the prevalence of common
pathogens endemic in the developing country.
Acute diarrhea in adults
The common causes of acute traveler’s diarrhea vary
from one geographical area to another.78–84 The most
frequently identified pathogen causing traveler’s diarrhea is toxigenic Escherichia coli, although in some parts
of the world (notably North Africa and South-east
Asia), Campylobacter infections appear to predominate.
Other common causative organisms include enteroaggregative E. coli, Salmonella spp., Shigella spp., rotavirus
and the Norwalk agent. Except for giardiasis, cryptosporidium and cyclosporidium, parasitic infections
are uncommon causes of traveler’s diarrhea.
The disease is usually short-lived, self-limited,
however, many of them are amenable to antibiotics.
Choice of antibiotics depends on epidemiologic data.
The same principle should apply in correcting dehydration from other types of diarrhea. Antidiarrheal
drugs can be given in conjunction with antibiotics.
A growing problem for travelers is the development
of antibiotic resistance in many bacterial pathogens;
examples include strains of Campylobacter resistant
to quinolones and strains of E. coli, Shigella, and Salmonella resistant to trimethoprim-sulfamethoxazole.
Antibiotic associated enterocolitis
Diarrhoea that occurs as a result of administered antibiotics which alter the normal intestinal flora and
increase the proliferation of Clostridium difficile, produce
enterotoxin A and B that cause enterocolitis and
pseudomembrane formation.85 Positive history of
antibiotics usage prior to the development of diarrhea
may raise the possibility of antibiotic associated enterocolitis, however, the use after the onset of diarrhea
usually does not suggest antibiotic associated enterocolitis. Onset of symptoms occurs either during antimicrobial administration or within four weeks after
treatment. While all antimicrobials may cause the syndrome, some drugs cause it more commonly than
others and some only rarely. The common causes of
antibiotic associated enterocolitis include clindamycin,
ampicillin, and the cephalosporins. The rare causes of
antibiotic associated enterocolitis are vancomycin,
metronidazole, and the aminoglycosides.
The clinical spectrum of antibiotics-associated enterocolitis is diverse. It ranges from mild loose watery
diarrhea to severe colitis causing bloody or dysenterylike diarrhea in the later course of the disease. In the
first week, diarrhea is usually watery, voluminous and
without gross blood or mucus. Later, it becomes bloody.
Other symptoms also vary considerably. At one end of
the spectrum are many patients with annoying diarrhea
with no severe systemic toxicity; while at the other end
are those with high and prolonged fever with abdominal pain. Abdominal pain can be severe with cramping,
especially at the left iliac fossa. Vomiting is uncommon
and dehydration is often mild except in very severe
cases. Examination of stool may reveal large numbers
of red blood cells and some leukocytes. Stool culture
for C. difficile needs anaerobic conditions and may take
several days to perform. It is usually more practical to
perform cytotoxin assay in the stool using ELISA, or
S69
tissue culture assay technique in confirming diagnosis.
Sigmoidoscopy or colonoscopy may reveal normal,
minimally erythematous colonic mucosa with some
edema, or granular, friable, or hemorrhagic mucosa
with typical pseudomembrane formation.
The course is highly variable. In patients with clinically mild disease, withdrawal of offending antibiotics
usually leads to prompt resolution of symptoms. Those
who have more protracted diarrhea usually need specific therapy. Oral rehdyration therapy is the mainstay
treatment to correct dehydration. Intravenous fluid may
be required in severe cases. Empiric metronidazole
250–500 mg four times daily should be administered
while waiting for the result of a cytotoxin study,
and should be continue for 10–14 days. If cytotoxin
study is positive and the patient does not get better
after a week of metronidazole, then vancomycin
125–250 mg/day should be substituted. Relapses or
reinfections are common and occur in as many as 20%
of cases. These patients can be treated with the same
treatment as given for the primary infection. Subsequent recurrences of antibiotic associated enterocolitis
are best managed with vancomycin plus rifampicin.
Antidiarrheal drugs have no advantage in treating
antibiotic-associated enterocolitis, except cholestyramine and probiotics, which can be helpful in chronic or
relapsing disease.
Hemorrhagic colitis (due to
Enterohaemorrhagic E. coli, EHEC or
Shiga Toxin Producing E. coli, STEC)
Hemorrhagic colitis, caused by enterohemorrhagic
Escherichia coli (EHEC), should always be a differential
diagnosis in patients who present with acute bloody
diarrhea, especially during an outbreak of food-borne
illness. Patients who present with non-bloody diarrhea
that progresses to bloody diarrhea should also raise the
possibility of EHEC diarrhea. Other prominent complaints include striking abdominal pain and tenderness
often in the absence of fever. In an outbreak situation,
some patients with EHEC infection may be asymptomatic and are only recognized during epidemiologic
surveillance in association with symptomatic cases. In
general, the mortality rate is 1–2%,86 although it may
be substantially higher in the young and the elderly.87
The most worrisome complication of EHEC infection
is the hemolytic–uremic syndrome (HUS),88 which
most frequently involves children between the ages of
5–10 years.89 Hemolytic-uremic syndrome is characterized by the triad of acute renal failure, microangiopathic
hemolytic anemia, and thrombocytopenia. Patients who
also have fever and neurologic symptoms are considered
to have the related disorder thrombotic thrombocytopenic purpura (TTP), which has also been associated
with E. coli O157:H7 infection.86,90 Hemolytic-uremic
syndrome usually begins 5–10 days after the onset of
diarrhea.86,90,91 The incidence of subclinical renal dysfunction is substantially higher, particularly in patients
with prolonged anuria during the initial presentation.92,93 Stool culture using sorbitol-MacConkey agar
S70
should be done in all suspected EHEC diarrhea. The
Centers for Disease Control and Prevention (CDC) has
recommended that all stools from patients with a
history of bloody diarrhea should be screened for E. coli
O157:H7 or Shiga toxin by direct stool examination.92
E. coli strains presumptively identified as E. coli
O157:H7 and Shiga toxin-positive stools should be sent
to a reference laboratory for confirmation. A number of
newer diagnostic approaches for EHEC infection
focuses on direct detection of Shiga toxins in stool, or
the use of DNA probes for detecting the toxin genes in
fecal isolates. One such assay, the Premier EHEC assay,
utilizes an enzyme-linked immunosorbent assay
(ELISA) to detect both Shiga toxin 1 and Shiga toxin
2 in stool.
The only current treatment of EHEC infection is
supportive, with monitoring for the development of
microangiopathic complications such as HUS. The
impact of antibiotic therapy on the duration of diarrhea
or on the subsequent occurrence of systemic complications is controversial. The use of antibiotics may actually increase the risk of HUS, perhaps by increasing
production or release of toxin.94 A number of new
approaches to therapy of EHEC infection are currently
being evaluated, but are not yet proven effective nor
available routinely. These include: toxin-binding
residues given orally and hyperimmune antitoxin
antisera.
Nosocomial diarrhea
Nosocomial diarrhea, that is acute diarrhea that occurs
in hospitalized patients, is an important problem in hospitals, and in critical care units in particular. Hospitalacquired diarrhea may be on an infectious or
non-infectious basis. Common non-infectious causes of
nosocomial diarrhea include food intolerance, drug
induced diarrhea, drug-induced changes in the fecal
flora, or changes secondary to enteral hyperalimentation.95,96 Infectious causes of nosocomial diarrhea are
due to eating food contaminated with enteric pathogens
or in outbreak situations. However, the major cause
of sporadic (non-epidemic) nosocomial diarrhea is
Clostridium difficile.96 All cases of nosocomial diarrhea
should be properly investigated with stool examination,
culture and C. difficile cytotoxin assay.97,98 Proper hydration together with dietary adjustment should immediately be employed. If possible, discontinuation of
offending drugs or antibiotics should be considered.
Empiric metronidazole can be started in patients with
a possibility of antibiotic associated enterocolitis. (See
antibiotic associated enterocolitis for details of this
infection). Systemic antibiotics may be necessary in
immunocompromised patients.
Outbreak diarrhea
Acute diarrhea that occurs in two or more persons from
the same exposure, assumed to be caused by the same
pathogens, is considered an outbreak.99–103
S Manatsathit et al.
In the situation in which there is a known outbreak
of an epidemiologically important enteric pathogen,
for example cholera, salmonella, shigella, campylobacter, EHEC (STEC), any acute diarrheas that occur in
the outbreak area should be managed as if they are
caused by the ‘outbreak pathogen’, no matter the severity of diarrhea. As in an outbreak situation, the disease
spectrum is often highly variable, ranging from very
mild to very severe. All acute diarrhea in the outbreak
area should be reported to the Area Health Authority
and proper epidemiologic investigation should be
employed. Rapid testing or a kit that is helpful in identifying the ‘outbreak pathogen’ should be used in the
field and further confirmation can be done later in a
reference center. Antibiotics that are known to be
effective in eradicating the pathogen should be empirically administered to all acute diarrhea cases in the outbreak area. The purpose is to contain the spreading
of the disease, not necessarily to shorten the clinical
course of diarrhea in that particular case. Epidemiologic
surveillance is necessary until the outbreak completely
subsides.
Institutional diarrhea
This is acute diarrhea that occurs in persons who stay
in an institution where there is a uniform population
with the same clinical or social setting, for example a
nursing home, a day-care center, a refugee camp,
etc.104–107
Any single case of acute diarrhea that occurs in an
institution should all be investigated by stool examination and culture, as there is risk of spreading among
inhabitants in the same institution and may progress to
an established outbreak of diarrhea. Apart from the
routine correction of dehydration, there should also be
isolation of the patient and an improvement of hygiene
and sanitation in the institution. Early empiric treatment with antibiotics may help to contain the suspected
enteropathogens. In patients with diarrhea due to salmonella, empiric antibiotic treatment may increase the
time of shedding of the organism by one to three weeks.
Antibiotics are usually not given to otherwise healthy
patients with milder forms of non-typhoid salmonellosis. The young or the elderly and patients with
immunocompromised are usually given antimicrobials
in intestinal salmonellosis. In confirmed groups, other
organisms may produce illness in individuals or as outbreaks. The cause of the illness generally requires laboratory study for identification.
Acute diarrhea in immunocompromised
patients
Acute diarrhea that occurs in an immunocompromised
host, who has been treated with immunosuppressive
agents or chemotherapy, or those with HIV infection,
autoimmune diseases, malignancy, especially hematologic malignancy, and acute graft-versus-host condition
are a special entity.108,109 Acute diarrhea that occurs in
Acute diarrhea in adults
these patients may easily lead to septicemia, hence early
antibiotic therapy during their course of diarrhea
should be instituted, no matter the type or severity of
the diarrhea.110–112 Apart from the hemodynamic
support, parenteral antibiotics are often needed. Bloody
diarrhea in immunocompromised patients may also be
caused by cytomegalovirus enteric infection.
Acute and chronic diarrhea that occurs in an HIV
infected person should receive special attention in terms
of investigation and management.113,114 HIV infected
persons, who are not yet immunocompromised or
having CD4 count > 500 cell/mm3, can be managed as
in the suggested algorithm (Fig. 1). But HIV infected
persons who are immunocompromised or their CD4
counts are < 500 cell/mm3, apart from doing routine
stool culture and examination, stool staining for AFB,
modified AFB, modified trichrome staining and C.
difficile cytotoxin assay should also be employed.
Blood cultures should be performed since enteropathogens and Mycobacterium-avium intracellulare
often produce bacteremia in immunocompromised
patients.115 Empiric treatment can be considered if the
nature of enteropathogens infecting these patients is
known.116 Specific treatment with antibiotics, if being
administered, should be given in a more prolonged
course to ensure the complete eradication of the
pathogen and prevent early relapse. Nutritional management is also required in this group of patients.
Gay bowel syndrome
This is a specific syndrome of acute diarrhea that occurs
in homosexual men who may or may not be infected
with HIV. Homosexual people are a unique group of
patients who are prone to diarrhea due to their sexual
activity, which is the primary method of transmission
for several important enteric parasitic diseases. The
majority of parasitic sexually transmitted diseases
involve protozoan pathogens; however, nematode and
arthropod illnesses are also included in this group. Oralanal and oral-genital sexual practices predispose male
homosexuals to infection with many enteric pathogens,
S71
including parasitic protozoans and helminths.The most
common of these parasitic infections are amebiasis,
caused by Entamoeba histolytica, and giardiasis caused
by Giardia lamblia.117 Both entities may cause acute or
chronic diarrhea, as well as other abdominal symptoms.
Most gay men with amebiasis are asymptomatic, and
invasive disease in this group is extremely rare. Both
amebiasis and giardiasis can be diagnosed on the
basis of microscopic examination of stool specimens,
although duodenal aspiration is occasionally necessary
to confirm a diagnosis of giardiasis. Metronidazole is
efficacious in the treatment of both amoebiasis and giardiasis. Other common causes of diarrhea in homosexual males include the spread of the organisms by
the fecal oral route (e.g. shigella, campylobacter,
salmonella) and those spread by receptive anal intercourse (e.g. Neisseria gonorrhoeae, Chlamydia trachomatis, Herpes simplex and Treponema pallidium.)
Acute diarrhea in septicemic
prone conditions
Acute diarrhea that occurs in a person who is prone to
septicemia due to the presence of some underlying conditions that are not truly immunocompromised conditions but were reported to have related higher incidence
of septicemia with diarrhea, or complications when
diarrhea occurs, for example cirrhosis, especially alcoholic cirrhosis, uncontrolled diabetes mellitus, patients
with heart valves, prosthesis, severe atherosclerosis with
aortic aneurysm, malignancy and uremia.118
There are several reports of-Non-O1 Vibrios septicemia in patients with cirrhosis.47,119,120 Uncontrolled
diabetes mellitus patients with diarrhea are prone to
gram negative septicemia.121 Patients with heart valve,
prosthesis, severe atherorosclerosis are prone to salmonella septicemia and lodging of salmonella infection at
the diseased heart valve and prosthesis.122,123 These
patients should be aware of the possibility of septicemia
and an early empiric parenteral antibiotic should be
administered from the first presentation.