Journal of Gastroenterology and Hepatology (2002) 17 (Suppl.

) S54S71

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. Lukes 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.35 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 0.52 episodes per person per year, and the corresponding gure 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-ve 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 countrys 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 denition

The nal 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 sacricing 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 amplication 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 denition 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 dened 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 dened, 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. Specic 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 specic acute diarrhea syndromes that may need a specically tailored approach and management, and where the general algorithm may need to be modied. For example, during epidemic acute diarrhea such as cholera, it is important to quickly identify the organism in the rst 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: sismt@mahidol.ac.th 2002 Blackwell Science Asia Pty Ltd

Acute diarrhea in adults

S55

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) - Travelers diarrhea - Antibiotic associated enterocolitis - Hemorhagic colitis (due to EHEC or STEC) - Outbreak diarrhea - Other specific conditions (see Table 2)

Vomiting

Toxin induced food poisoning or viral gastroenteritis Replace deficit with ORS/IVF Maintain hydration with ORT

Diarrhea

Watery Diarrhea

Bloody Diarrhea

Replace deficit with ORS/IVF Maintain hydration with ORT In Cholera-endemic area Stool examination, DFM,*
Culture/Sensitivity

Yes

Clinical dehydration No

Stool Examination, culture/sensitivity1 If EHEC not suggested Empiric ATB for 35 d.2

E.histolytica trophozoites

Metronidazole plus cysticidal drug

Maintain hydration with ORT Consider antidiarrheals for 48 hrs.

DFM +ve

DFMve, wait for culture result

Not improved

Not improved

ATB for cholora

Consider ATB if pathogen identified

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 eld microscopy (if not available, look for shooting bacteria under light microscopy); ATB, antibiotics; ORT, oral rehydration therapy; IVF, intravenous uid.

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. Inammatory bowel disease Ischemic enterocolitis Mesenteric artery/venous occlusion

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-

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.

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 specic pathogens are more common during a specic 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 patients immune status should be called to the physicians attention, such as practices that may predispose the patient to HIV infection, history of administration of immunosuppressive drugs, steroids, and chemotherapy.

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 classied, 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 624 h, diarrhea occurs 27 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 814 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 nding in the other forms of food poisoning. Foods that are likely to be contaminated with toxin or infectious organisms
Table 2 Specic acute diarrhea syndromes that require special consideration Acute diarrhea in the elderly (age 65-years-old) Travelers 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

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 lling. 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

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 4872 h.11 Symptomatic and supportive treatment is usually sufcient. If the patient can drink, oral rehydration therapy is highly encouraged. If vomiting is severe and dehydration is signicant, intravenous therapy may be necessary. Antiemetics, such as metocloparmide, are not effective if given orally, but intramuscular injection may be efcient. Abdominal cramping pain may respond to antispasmodics, for example hyoscine, hyoscyamine and dicyclomine.

S57
Table 3 Enteropathogens responsible for infectious diarrhea (modied from Farthing M.) Watery diarrhea Bloody diarrhea

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 difcile Plesiomonas shigelloides Protozoa Giardia intestinalis Cryptosporidium parvum Microsporidia Isospora belli Cyclospora cayetanensis Entamoeba histolytica Balantidium coli Helminths Strongyloides stercoralis Schistosoma spp.

+ + + + + + + + + + + + + + + + + + + + + + + + + + + +

+ + + + + + + + + + + + +

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 37.5C or 99.5F) 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 2448 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 and Vibrio 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 difcile may also present as watery diarrhea, especially in the initial stages of their course (see Table 3).

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 classied 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 tion, and does not include mild diarrhea or mild dehydration. All cases of acute diarrhea would have dehydration due to loss of uid and electrolytes. Even mild diarrhea would have some degree of dehydration, but this may be difcult to assess quantitatively. Adults normally have better compensatory mechanisms than children through the larger body uid reserve, the better kidney compensatory mechanisms, and better response to correct thirst. Together with poorer tissue elasticity and slower shift of extra cellular uid, 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).

S Manatsathit et al. 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 eld microscopy (DFM) and stool culture should be done in all cases. Stool examination with ne 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, notication 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 conrm in all cases (see Appendix). Treatment: The treatment of watery diarrhea should focus mainly on uid 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 uid repletion and supportive care can obviate the high mortality that is associated with the disease. Also if vomiting is severe and the decit cannot be replaced solely by ORS, intravenous uids in the form of Ringer lactate will be required. In moderate to severe diarrhea, at least half of the calculated decit should be replaced within 4 h and the rest is to be replaced within 24 h.24 Evaluation of uid and electrolyte decit is crucial in calculating the amount of uids to replace. Hence, stool volume loss should be closely monitored

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 Classication of severity of dehydration Mild Subjective General state Ability to perform daily activities

Moderate

Severe

Alert, active, up and about Able to perform daily activities without difculty

Thirst Objective signs Pulse Blood pressure Postural hypotension Jugular venous pressure Dry mucosa (mouth, tongue) Skin turgor Sunken eye balls

Not increased Normal Normal No Normal No Good No

Weak, lethargic. Able to sit and walk Able to perform daily activities with some difculty, e.g. stays away from work, needs support Increased thirst Tachycardia Normal or decrease 1020 mmHg systolic Yes or no Normal or slightly at Slight Fair Minimal

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 difcult to estimate accurately the amount of decit 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 ciprooxacin 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 benet in reducing stool volume loss and shortening the clinical course in adult patients with cholera.26

S59 cells/HPF.27 These cases usually are not accompanied with fever.

Treatment: As dehydration is often mild, the need for uid 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 uid decits. Intravenous uid 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 scientic information regarding efcacy, 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 exneri, 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 difcile, 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 38.5C. Initially, these patients may pass watery stools that rapidly progresses to bloody diarrhea and dysentery. Dysentery is characterized by the frequent passage (usually 1030 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 patients3133 (see Appendix).

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 48 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 rst 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

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 uoroquinolones is preferred. Noroxacin 800 mg/day, ciprooxacin 1000 mg/day or levooxacin 500 mg/day for 35 days should be adequate for healthy adults. For geriatric patients, or septicemic prone conditions, ooxacin or ciprooxacin 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.

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 specic 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-specic 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 identication for Vibrio cholerae serotype and serogrouping should be done, together with the identications 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 travelers 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 difcile 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 812 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.

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-eld 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, ne 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.

Unresolved diarrhea
All patients who do not improve after rehydration, with or without antidiarrheals and/or empiric antibiotics, should require re-evaluation after 35 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 (> 38.5C), if their stage of

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 rst few days of onset of illness. In most such individ-

Acute diarrhea in adults 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 rst visit. In cases of bloody diarrhea without an identiable pathogen, which do not improve after empiric treatment, further investigation by doing sigmoidoscopy or colonoscopy together with biopsy is usually necessary.

S61 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 conrm the efcacy 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.

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

Oral rehydration Selective antibiotics for known pathogens

Whenever stool examination and culture results are available, treatment should be as selective and specic In this article, the term ORS (Oral Rehydration Salts Solution) and ORT (Oral Rehydration Therapy) are used.To avoid confusion, clarication of these terms are presented below.

Table 5 Organism

Recommended antibiotics against specic enteric pathogens Suggested antibiotics Tetracycline, 500 mg q.i.d. 3 d Alternative antibiotics Doxycycline, 300 mg single dose TMP-SMZ, 160800 mg b.i.d. 3 d Fluoroquinolone* 3 d Doxycycline, 300 mg single dose TMP-SMZ, 160800 mg b.i.d. 3 d Fluoroquinolone* 3 d Doxycycline, 300 mg single dose, Fluoroquinolone* 3 d Ceftazidime# 1 g q 6 h 57 d Doxycycline, 300 mg single dose Fluoroquinolone* 3 d Gentamicin#, 80 mg 57 d Cefotaxime#, 1 g q.i.d. 57 d TMP-SMZ, 160800 mg b.i.d. 3 d Nalidixic acid 1 g/day 5 d Ceftriaxone#, 1 g b.i.d. 57 d Azithromycin 250 mg single dose TMP-SMZ, 160800 mg b.i.d. 57 d (if susceptible) Ceftriaxone#, 1 g b.i.d. 714 d TMP-SMZ, 160800 mg b.i.d. 3 d (if susceptible) TMP-SMZ, 160800 mg b.i.d. 3 d (if susceptible) TMP-SMZ, 160800 mg b.i.d. 3 d (if susceptible)

Vibrio cholera O1

Vibrio O139

Tetracycline, 500 mg q.i.d. 3 d

Other non-O1 Vibrio spp.46 Vibrio parahemolyticus47

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 Fluoroquinolone* 3 d

Shigella species

Non-typhoidal species of Salmonella Aeromonas species

Plesiomonas species

Enterotoxigenic Escherichia coli

Antibiotics are usually not required, except in certain situations.c Fluoroquinolone* 57 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, 160800 mg b.i.d. 3 d

S62
Table 5 Organism Enteropathogenic Escherichia coli (continued) Suggested 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, 250500 mg q.i.d. 1014 d

S Manatsathit et al.

Alternative antibiotics TMP-SMZ, 160800 mg b.i.d. 3 d (if susceptible)

Enteroinvasive Escherichia coli Enteroaggregative Escherichia coli48 Enterohaemorrhagic Escherichia coli (STEC) Campylobacter species

TMP-SMZ, 160800 mg b.i.d. 3 d (if susceptible)

Fluoroquinolone* 5 d

Yersinia species

Toxigenic Clostridium difcile

a

Combination of doxycycline and aminoglycoside, or TMP-SMZ, or uoroquinolone Vancomycin 125250 mg q.i.d. 10-14 d

antibiotics may be required in septicemic prone conditions e.g. cirrhosis, or immunocompromised hosts antibiotics may be required in severely ill patients, or travelers 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, travelers diarrhea, or immunocompromised hosts, or septicemic prone conditions, or uncontrolled diabetes mellitus. f antibiotics may be required in severely ill patients, travelers diarrhea g antibiotics may be required in severely ill patients, or associated bacteremia, or when bacteremia is suspected, or immunocompromised hosts, *uoroquinolone, for example 300 mg ooxacin, 400 mg noroxacin, or 500 mg ciprooxacin 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 1.52 times the estimated amount of decit plus concurrent loss.

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-benet 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 briey reviewed, so that physicians can decide which to use by judging from their efcacy, side-effects, indications and contra-indications based on the available literature. Antidiarrheal drugs are grouped and discussed under the following topics.

Intravenous uid replacement

For initial management of severely dehydrated or hypovolemic shock patients, immediate intravenous uid replacement is essential. Patients with moderate or milder degree of dehydration may also need intravenous uid 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. Ringers 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 decit. The total uid decit in severely dehydrated patients can be replaced safely within the rst 4 h of therapy, half within the rst hour.52 The volume of uid 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 uid intake equal to the ongoing loss. However, patients with continued large-volume diarrhea might require prolonged intravenous treatment to keep up with gastrointestinal uid 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.

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.5355 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 signicant 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 specic causes of diarrhea, in many cases, causes that are specic and potentially treatable are often not identiable. Identication 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 uid 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 nancial cost of the drugs.The cost-benet 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 nancial 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 xed to intestinal mucosa. Their efcacy 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.5961 In clinical trials, they can increase stool consistency and decrease stool frequency, but cannot reduce the amount of uid 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.

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 reex. 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 efcacy 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 signicant 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.

Probiotics
Probiotics are non-pathogenic organisms, for example Lactobacillus acidophilus and Saccharomyces boulardii, which multiply in the patients 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 benecial for intestine recovery, and increase the rate of uid and electrolyte absorption. In children, there are studies which show that the use of probiotics could reduce the clinical course of acute diarrhea.6264 In adults, they are used mainly in chronic diarrhea and relapse of antibiotic associated enterocolitis.65

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 scientic data to support or conrm the efcacy 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
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

CONCLUSION
Acute diarrhea in adults is a common every-day condition all over the world. Besides acute infectious diarrhea, the denition 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 specic situations of acute diarrhea that deserve to be approached differently, patients are classied as having predominately diarrhea or predominately vomiting.The diarrhea predominant group is further classied 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 eld microscopy conrmed 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 rst visit and specic pathogens causing diarrhea are identied, specic 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.

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15 Stenhoff MC, Douglas RGJ, Greenberg HB, Callahan DR. Bismuth subsalicylate therapy of viral gastroenteritis. Gastroenterology 1980; 78: 14959. 16 Bhattacharya SK, Bhattacharya MK, Nair GB et al. Clinical prole of acute diarrhoea cases infected with the new epidemic strain of Vibrio cholerae O139: designation of the disease as cholera. J. Infect. 1993; 27: 1115. 17 Campos E, Bolanos H, Acuna MT et al. Vibrio mimicus diarrhoea following ingestion of raw turtle eggs. Appl. Environ. Microbiol. 1996; 62: 11414. 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: 458. 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: 37885. 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: 27580. 21 Keen MF, Bujalski L. The diagnosis and treatment of cholera. Nurse Pract. 1992; 17: 536. 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: 8826. 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: 93645. 24 Seas C, DuPont HL,Valdez. LM et al. Practical guideline for treatment of cholera. Drugs 1996; 51: 96673. 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: 30813. 27 Alvarado T. Fecal leucocytes in patients with infectious diarrhoea. Trans. R. Soc.Trop. Med. Hyg 1983; 77: 31620. 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: 77382. 29 Kain KC, Kelly MT. Clinical features, epidemiology, and treatment of Plesiomonas shigelloides diarrhea. J. Clin. Microbiol. 1989; 27: 9981001. 30 Siegel D, Cohen PT, Neighbor M et al. Predictive value of stool examination in acute diarrhea. Arch. Pathol. Lab. Med. 1987; 111: 7158. 31 Bennett RG, Greenough WB. Approach to acute diarrhea in the elderly. Gastroenterol. Clin. North Am. 1993; 22 (3): 51733. 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: 32804. 33 Ramakrishna BS. Gastrointestinal infections in the elderly. In: Sharma OP ed. Geriatrics and. Gerontology: ANB Publishers. New Delhi, 1999; 18695. 34 Thorne GM. Diagnosis of infectious diarrheal diseases: infectious diarrhea. Infect. Dis. Clin. North Am. 1988; 2: 74774.

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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: 77582. 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: 38894. 90 Su C, Brandt LJ. Escherichia coli O157: H7 infection in humans. Ann. Intern. Med. 1995; 123: 698714. 91 Bell BP, Goldoft M, Grifn. 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: 134953. 92 Seigler RL, Milligan MK, Burningham TH et al. Long-term outcome and prognostic indicators in the hemolyticuremic syndrome. J. Pediatr. 1991; 118: 195200. 93 Fitzpatrick MM, Shah V, Trompeter RS, Dillon MJ, Barratt TM. Long-term renal outcome of childhood haemolytic uraemic syndrome. BMJ 1991; 303: 48992. 94 Walterspiel JN, Ashkenazi S, Morrow AL et al. Effect of subinhibitory concentrations of antibiotics on extracellular Shiga-like toxin I. Infection 1992; 20: 259. 95 McFarland LV. Epidemiology of infectious and iatrogenic nosocomial diarrhoea in a cohort of general medicine patients. Am. J. Infect. Control 1995; 23: 295305. 96 Cunha BA. Nosocomial diarrhoea. Crit. Care Clin. 1998; 14: 32938. 97 Mylotte JM, Graham R., Kahler L,Young L, Goodnough S. Epidemiology of nosocomial infection and resistant organisms in patients admitted for the rst time to an acute rehabilitation unit. Clin. Infect. Dis. 2000; 30: 42532. 98 Cartmill TD, Shrimpton SB, Panigrahi H, Khanna V, Brown R., Poxton IR. Nosocomial diarrhoea due to a single strain of Clostridium difcile: 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: 819. 100 Daniels NA, Bergmire-Sweat DA, Schwab KJ et al. A foodborne outbreak of gastroenteritis associated with Norwalk-like viruses: rst molecular traceback to deli sandwiches contaminated during preparation. J. Infect. Dis. 2000; 181: 146770. 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: 625. 102 Hedberg CW, Levine WC, White KE et al. An international foodborne outbreak of shigellosis associated with a commercial airline. JAMA 1992; 268: 320812. 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: 3114.

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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: 97107. 105 Bacillus cereus food poisoning associated with fried rice at two child day care centers-Virginia 1993. MMWR Morb. Mortal.Wkly Rep. 1994; 1778. 106 Emont SL, Cote TR, Dwyer DM, Horan JM. Gastroenteritis outbreak in a Maryland nursing home. Md Med. J. 1993; 42: 1099103. 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: M2526. 108 Asplund S, Gramlich TL. Chronic mucosal changes of the colon in graft-versus-host disease. Mod. Pathol. 1998; 11: 5135. 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. Efcacy of chlorhexidine gluconate use in the prevention of perirectal infections in patients with acute leukemia. Oncol. Nurs. Forum 1991; 18: 120713. 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: 132831. 112 Poulos JE, Cancio M, Conrad P, Nord HJ, Altus P. Non 01 Vibrio cholerae septicemia and culture negative neutrocytic ascites in a patient with chronic liver disease. J. Fla. Med. Assoc. 1994; 81: 6768. 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: 1522. 114 Weber R., Ledergerber B, Zbinden R. et al. Enteric infections and diarrhoea in human immunodeciency virusinfected persons: prospective community-based cohort study. Swiss HIV Cohort Study. Arch. Intern. Med. 1999; 159: 147380. 115 Du Pont HL, Marshall GD. HIV-associated diarrhea and wasting. Lancet 1995; 346: 3526. 116 Ramakrishna BS. Prevalence of intestinal pathogens in HIV patients with diarrhea: implications for treatment. Indian J. Pediatr. 1999; 66: 2936. 117 Levine GI. Sexually transmitted parasitic diseases. Prim. Care 1991; 18: 10128. 118 Gagarin VV. Acute disorders of the mesenteric circulation among heart defect patients. Kardiologiia 1984; 24: 814. 119 Chan TY, Chow DP, Ng KC, Pang KW, McBride GA. Vibrio vulnicus septicemia in a patient with liver cirrhosis. Southeast Asian J.Trop Med. Public Health 1994; 25: 21516. 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: 312. 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.

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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: 3859. 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: 1537.

APPENDIX
The following specic conditions of acute diarrhea are specically mentioned here as there are theoretical basis and scientic 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 conned 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 difcile 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.

Travelers diarrhea
This is a specic 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 travelers diarrhea vary from one geographical area to another.7884 The most frequently identied pathogen causing travelers 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 travelers 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.

S69 tissue culture assay technique in conrming 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 specic therapy. Oral rehdyration therapy is the mainstay treatment to correct dehydration. Intravenous uid may be required in severe cases. Empiric metronidazole 250500 mg four times daily should be administered while waiting for the result of a cytotoxin study, and should be continue for 1014 days. If cytotoxin study is positive and the patient does not get better after a week of metronidazole, then vancomycin 125250 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.

Antibiotic associated enterocolitis

Diarrhoea that occurs as a result of administered antibiotics which alter the normal intestinal ora and increase the proliferation of Clostridium difcile, 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 rst 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. difcile 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

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 12%,86 although it may be substantially higher in the young and the elderly.87 The most worrisome complication of EHEC infection is the hemolyticuremic syndrome (HUS),88 which most frequently involves children between the ages of 510 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 510 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 identied as E. coli O157:H7 and Shiga toxin-positive stools should be sent to a reference laboratory for conrmation. 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.

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 eld and further conrmation 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.104107 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 conrmed groups, other organisms may produce illness in individuals or as outbreaks. The cause of the illness generally requires laboratory study for identication.

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 ora, 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 difcile.96 All cases of nosocomial diarrhea should be properly investigated with stool examination, culture and C. difcile 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.

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

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.99103

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.110112 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, modied AFB, modied trichrome staining and C. difcile 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 Specic 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.

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 conrm a diagnosis of giardiasis. Metronidazole is efcacious 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 rst presentation.

Gay bowel syndrome

This is a specic 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,