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Journal of Gastroenterology and Hepatology (2002) 17 (Suppl.) S54–S71
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
provide a complete document that would be applicableto the case management of diarrhea. However, some Acute diarrhea in adults is one of the most common explanation and amplification is necessary to clarify the diagnoses in general practice,1,2 and is responsible for terms and phrases that have been used, as well as to considerable morbidity around the world.3–5 While explain the basis for certain decision pathways in the acute diarrhea is perceived as a major cause of child- hood mortality in developing countries, adult mortality Adult: The definition of ‘adult’ varies from one
from diarrhea is also not uncommon particularly during country to another. As applied in this guideline, the epidemics of diarrhea. Contaminated food and water, term ‘adult’ refers to someone who is of age 12 years or together with unhygienic eating habits, account for the continuing high prevalence of acute diarrhea in adults.
Acute diarrhea: This is defined as the passage of three
In industrialized countries, the incidence of acute or more than three loose or watery stool in 24 h, or diarrhea is estimated to average 0.5–2 episodes per passage of one or more bloody stool. Acute diarrhea person per year, and the corresponding figure could be refers to illness not lasting longer than 14 days.
much higher in developing and underdeveloped coun- Other conditions that may present as acute diar-
tries. In the USA, with a population of around 200 rhea: ‘Acute diarrhea’ is a clinical syndrome that is
million, about 99 million episodes of acute diarrhea commonly understood to refer to infective gastroen- occur every year in adults. Twenty-five percent of hos- teritis. However, as defined, acute diarrhea may be a pitalizations in the USA were due to diarrhea and 85% symptom of other intra-abdominal or systemic illnesses.
of the mortality associated with diarrhea occurred in the These other clinical conditions may require particular elderly (> 65 years old).6 It accounts for a large amount investigations and management, and will need to be of economic loss and a waste of a country’s resources recognized and excluded at the outset. Careful history and labor forces in caring for this group of patients.7 It and physical examination is necessary to exclude these is hoped that the development of this guideline will be conditions from the commonly understood ‘acute diar- able to provide measures for general practitioners and rhea’. Special attention should be paid to exclude signs health care workers around the world to effectively care of peritonism or peritonitis, which will indicate serious for adult diarrhea patients so that the mortality and illnesses that might require surgical care. Examples of these diverse clinical conditions are presented in
Table 1.
Specific conditions of acute diarrhea that require
Algorithm and definition
special consideration: Although the term ‘acute
diarrhea’ commonly refers to infectious, toxin-induced
The final algorithm that was developed for the manage- and drug-induced diarrhea, there are specific acute ment of adult diarrhea was the result of intensive diarrhea syndromes that may need a specifically tailored discussion among the experts. It particularly empha- approach and management, and where the general algo- sized simplicity, feasibility and availability of options.
rithm may need to be modified. For example, during It tries to be as general as possible without sacrificing epidemic acute diarrhea such as cholera, it is important the basic principles and theoretical background of to quickly identify the organism in the first patients pre- sound management. The algorithm, in itself, should senting 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] Specific diarrhea requiring special consideration
- Acute diarrhea in the elderly (age > 65 years)
Other conditions which
- Hemorhagic colitis (due to EHEC or STEC) may present as acute
diarrhea (see Table
Vomiting
Diarrhea
Watery Diarrhea
Bloody Diarrhea
In Cholera-endemic area
∑ Consider antidiarrheals for 48 hrs.
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 (selectantibiotics 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, intravenousfluid.
Conditions presenting as acute diarrhea with or HISTORY AND PHYSICAL
without signs of peritonitis that should be excluded in a 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 physicalexamination is therefore necessary in these patients.
Special attention should be paid to excluding Peritonitis secondary to bowel perforation conditions that may require a different approach and Systemic infections: for example malaria, measles, typhoid, Inflammatory bowel diseaseIschemic enterocolitisMesenteric artery/venous occlusion History taking
In the history, it is essential to gather the followinginformation: age, onset and duration of diarrhea, char- sures that will stop the outbreak. Acute diarrhea in the acter of the stool (watery, loose or bloody), frequency elderly needs to be treated in a different manner from and volume of stool, progression of severity of diarrhea, that of younger people because of the possibility of com- presence and severity of vomiting, presence of fever, its plications relating to compromised cardiac and cerebral severity and duration, abdominal pain and its location circulation. A number of these clinical entities are listed and character, cramps, and tenesmus. The severity of in Table 2, and these are discussed in greater detail in diarrhea may be assessed in adults by the degree of dis- turbance of daily life and activities, debility, thirst, dizzi- ness, and syncope. The time of last urination should be the character of stool and accurately assess the type of noted in patients with dehydrating diarrhea.
diarrhea, whether it is watery or bloody. This is partic- Occurrence of diarrhea after eating a contaminated ularly helpful in situations in which patients, especially meal, the time interval between ingestion and develop- the elderly or those with poor eyesight, might not be ment of diarrhea, and the occurrence of illness in others who also partook of the meal are pointers to a bacter-ial cause of the illness.8 The source of water supply maybe helpful as evidence of a common-source outbreak.9 MAJOR PRESENTATION: VOMITING
The location in which the patient develops diarrhea maybe predictive of the causative organism, for example at Diarrhoea is the predominating symptom in most home, in hospital or in an institution. History of recent patients presenting as ‘acute diarrhea’. Having excluded travel and the area travelled, may also be helpful. If the other conditions listed in Tables 1 and 2, we are left there is research to suggest that specific pathogens are with a group of illnesses that comprise what is com- more common during a specific season, this is an addi- monly understood as ‘acute diarrhea’. These are further tional factor of which to remain aware.
classified, on the basis of the stool character, as having It is always worthwhile to exclude the non-infectious either watery diarrhea or bloody diarrhea. This is one causes of acute diarrhea and osmotic diarrhea, for of the decision points in the algorithm, and is discussed example drugs and toxins. One should inquire if the further. On the other hand, there are some patients with patient has recently been taking medications or sub- ‘acute diarrhea’ in whom vomiting overshadows stances that can cause diarrhea, for example laxatives, diarrhea as a symptom. In these patients, one should antacids containing calcium or magnesium, colchicines, suspect that the illness is caused either by food poison- antibiotics, alcoholic beverages and sorbitol containing ing (induced by preformed bacterial toxin) or viral gums. If such a history is obtained, the suspected offending substance should be stopped before proceed-ing to any further evaluation.
In addition, it is important to take into account any underlying diseases that may be present, such as dia- Bacterial toxin induced food poisoning
betes, hypertension, heart disease, chronic lung disease,chronic renal failure or cirrhosis, because these could In patients with bacterial preformed heat-stable toxin complicate the management of diarrhea. Any condition induced food poisoning, the incubation period is that affects the patient’s immune status should be called usually 6–24 h, diarrhea occurs 2–7 h after eating the to the physician’s attention, such as practices that contaminated food. These patients usually present with may predispose the patient to HIV infection, history of intense nausea and severe vomiting as the major symp- administration of immunosuppressive drugs, steroids, toms. Diarrhoea may follow and usually is not so severe.
Abdominal pain may also be present and is usuallycolicky in nature. Most patients are afebrile and notseverely dehydrated unless vomiting or diarrhea isintense. Clostridium perfringens is also a food-borne Physical examination
disease with a characteristic incubation period of8–14 h. C. perfringens differs clinically from food poi- In the adult with diarrhea, it is important to look for soning due to Staphylococcus aureus and Bacillus cereus signs of dehydration, including examination of the in the longer incubation period and in clinical symp- pulse, blood pressure (standing and sitting), jugular toms. Vomiting is unusual in C. perfringens food-borne venous pressure, skin turgor, mucosal dryness, for disease and it is the most important clinical finding in example in the mouth and lips, evidence of sunken eye the other forms of food poisoning. Foods that are likely to be contaminated with toxin or infectious organisms It should be stressed that, regardless of the severity of diarrhea, abdominal examination is strongly recom-mended for every patient. Both light and deep palpa- Specific acute diarrhea syndromes that require tion should be carefully performed to exclude signs of peritonitis. Although minimal tenderness to deep pal-pation can be found in dysentery, it should be seriously Acute diarrhea in the elderly (age ≥ 65-years-old) observed and these patients must be closely monitored, because some surgical or serious medical conditions, for example appendicitis, diverticulitis, adnexitis, pan- Hemorrhagic colitis (due to enterohaemorrhagic E. coli, creatitis and ischemic colitis, may present as acute EHEC or Shiga-toxin producing E. coli, STEC) diarrhea. In acute diarrhea, guarding, rigidity and re- bound tenderness should not be present. If they are Acute diarrhea in immunocompromised hosts present at all, further investigations and appropriate Rectal examination should be part of the initial exam- ination in every case, especially in patients over 50 years Acute diarrhea in septicemia prone conditions of age.10 This allows the physician to see with certainty are cake, bread and cooked rice that have been left for Enteropathogens responsible for infectious diarrhea 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 highlyencouraged. If vomiting is severe and dehydration is sig- nificant, intravenous therapy may be necessary. Anti- emetics, such as metocloparmide, are not effective if given orally, but intramuscular injection may be effi- cient. Abdominal cramping pain may respond to anti- spasmodics, for example hyoscine, hyoscyamine and Bacteria
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 affectedindividuals. 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 Protozoa
week or longer.13 In general, oral rehydration treatment is adequate and only in rare cases intravenous rehydra- tion may be needed.14 Bismuth subsalicylate has been shown to improve the clinical symptoms of viral MAJOR PRESENTATION:
Helminths
DIARRHEA
ETEC, enterotoxigenic Escherichia coli; EPEC, enteropath- Watery diarrhea, that is, stool of decreased form from ogenic E. coli; EAggEC, enteroaggregative E. coli; EIEC, normal-looking, semiformed to loose or watery, without enteroinvasive E. coli; EHEC, enterohaemorrhagic E. coli. the presence of blood, is often the clinical presentationof enterotoxin induced diarrhea. Examples of such diar-rhea include cholera caused by Vibrio cholerae andVibrioO139, and diarrhea due to non-O1 vibrios, enterotoxi- Bloody diarrhea is the clinical presentation of severe genic Escherichia coli, and enteropathogenic E. coli.
bacterial colitis, which is caused by invasive enteric Some cases of infection with Vibrio parahemolyticus, pathogens, for example Shigella spp., Salmonella spp., Salmonella, Aeromona spp., Pleisiomona spp., Campy- Campylobacter jejuni, Yersinia enterocolitica, enteroinva- lobacter jejuni, Yersinia enterocolitica and Clostridium dif- sive E. coli, enterohemorrhagic E. coli, Entamoeba his- ficile may also present as watery diarrhea, especially in tolytica and Balantidium coli. Some cases of Vibrio the initial stages of their course (see Table 3).
parahemolyticus, Aeromona spp., and Plesiomona spp.
may also present as bloody diarrhea, especially later inthe course of acute diarrhea (see Table 3).
Bloody diarrheaDiarrhoea where the stool on macroscopic observationcontains blood mixed up with feces or inseparable from Clinical dehydration
the stool is classified as bloody diarrhea. Microscopi-cally, the feces generally contain numerous red blood For the purpose of this guideline, the term ‘clinical dehydration’ refers to moderate and/or severe dehydra- tion, and does not include mild diarrhea or mild other features are also important, for example the very abrupt onset of acute diarrhea that occurs in a matter All cases of acute diarrhea would have dehydration of hours, the rapid progression to profound dehydra- due to loss of fluid and electrolytes. Even mild diarrhea tion, the absence of fever and abdominal pain, and the would have some degree of dehydration, but this may presence of muscle cramps.16,21,22 In the obvious cases, be difficult to assess quantitatively. Adults normally stools are often greenish-yellow clear watery with very have better compensatory mechanisms than children little food residue. Signs of dehydration should be through the larger body fluid reserve, the better kidney present and sometimes are very prominent. Dark field compensatory mechanisms, and better response to microscopy (DFM) and stool culture should be done correct thirst. Together with poorer tissue elasticity in all cases. Stool examination with fine microscopic and slower shift of extra cellular fluid, the clinical adjustment could also reveal shooting bacteria, but signs of dehydration in adults would be less obvious there are no red blood cells or white blood cells. In than in children. Severity of dehydration does not nonendemic areas, once DFM or stool culture is posi- always correlate with severity of diarrhea. Some may tive for cholera, notification of the area health author- rely on the subjective symptoms alone to classify ity should be done as soon as possible.
severity of diarrhea while it is more reliable to evaluate It should be noted that in endemic areas, during out- the severity of dehydration from objective signs. The breaks or seasonal epidemics of cholera, watery diarrhea proper assessment of severity of dehydration should of all severity should be treated as cholera and stool utilize both subjective and objective evidence (see culture should be done to confirm in all cases (see Treatment: The treatment of watery diarrhea should
Watery diarrhea with clinical dehydration focus mainly on fluid and electrolyte replacement. In In general, severe watery diarrhea with severe dehydra- patients with mild dehydration, and with little or no tion is mostly caused by V. cholerae serogroup O1. There vomiting, oral rehydration therapy using oral rehydra- are also other organisms that cause a similar clinical tion salts solution (ORS) should be administered at picture as cholera. They are Vibrio O139,16 other- approximately 1.5 times the volume of stool loss in Non-O1 vibios17 and sometimes Vibrio parahemolyticus, 24 h without discontinuing dietary intake.23 In moder- ate to severe dehydration, prompt aggressive intra- Although diarrhea caused by these organisms is often venous fluid repletion and supportive care can obviate milder than cholera, more severe cases may occur, the high mortality that is associated with the disease.
which should be treated in the same fashion as severe Also if vomiting is severe and the deficit cannot be watery diarrhea. On the other hand, it should be noted replaced solely by ORS, intravenous fluids in the form that during epidemics, or even in an endemic area for of Ringer lactate will be required. In moderate to severe cholera, patients with cholera may be found to have only diarrhea, at least half of the calculated deficit should be mild diarrhea, and they should be managed differently replaced within 4 h and the rest is to be replaced within from the suggested algorithm (see Appendix).
24 h.24 Evaluation of fluid and electrolyte deficit is Although severe profuse watery diarrhea alone is crucial in calculating the amount of fluids to replace.
highly suggestive of cholera, it should be stressed that Hence, stool volume loss should be closely monitored Classification of severity of dehydration Subjective
Objective signs
and, if possible, weighed or accurately measured. In cells/HPF.27 These cases usually are not accompanied those patients who are not sick enough and still can go to toilets on their own, it may be difficult to estimateaccurately the amount of deficit and ongoing loss.
Where culturally acceptable the use of ‘cholera cots’ can Treatment: As dehydration is often mild, the need for
be very helpful to monitor the amount of ongoing loss. fluid and electrolytes replacement may be less pressing If cholera cots are not available, it may be safer to than in the group with clinical dehydration. Neverthe- replace twice the amount of estimated loss and closely less, rehydration remains the mainstay of treatment in monitor the status of hydration of the patient.
this group of patients. As the disease is dynamic and Antibiotics, when given to cholera patients, reduce mild dehydration may progress to more severe dehy- stool volume loss and shorten the clinical course.25 If dration, early hydration with oral rehydration therapy there is recent epidemiological data available, the (ORT) should be encouraged to prevent fluid deficits.
empiric antibiotics should be given according to the Intravenous fluid replacement is often not needed.
sensitivity of Vibrio cholerae in the region. In cases where Administration of antibiotics is unnecessary and not antibiogram is not available, tetracycline 2 g daily for recommended. Antidiarrheals can be allowed and lop- 3 days should be the treatment. Alternatively, doxycy- eramide has been recommended for use as self- cline 300 mg as a single oral dose, or 100 mg twice medication in adults with mild acute diarrhea.28 (A brief daily for 3 days, and ciprofloxacin 500 mg twice daily review of scientific information regarding efficacy, side- for 3 days (especially in regions where resistance effects and precautions for the use of these antidiar- to tetracycline is greater than 20%), have all been recommended. For pregnant women, furazolidone Particular attention should be paid to geriatric 400 mg/day for 3 days has been suggested. Antidiarrheal patients over the age of 65 years, immunocompromised drugs may be somewhat effective in reducing enteric patients, and patients with conditions predisposing to symptoms, but they play a minor role in the treatment septicemia. Patients in these categories will need antibi- of watery diarrhea and cannot be routinely recom- otics, usually orally administered but sometimes sys- mended. (Loperamide is not indicated for patients with severe watery diarrhea, for example cholera, but forwatery diarrhea in travelers, loperamide can be veryhelpful). Treatment should rely only on rehydrationtherapy and antibiotics only. Recently the use of resis-tant starch has been shown to be of benefit in reducing Bloody diarrhea
stool volume loss and shortening the clinical course inadult patients with cholera.26 Most acute bloody diarrhea is caused by Shigella spp.
and Campylobacter jejuni. Shigella dysenteriae and Shigellaflexneri, often produce a more severe disease with high Watery diarrhea without dehydration fever, while Shigella boydii and Shigella sonnei usually Patients in this group comprise the majority of cases of cause a milder disease. Other enteric pathogens pro- acute diarrhea in adults. They are often mild and are ducing bloody diarrhea include Salmonella enteritidis, not accompanied with signs of dehydration.They repre- Yersinia enterocolitica, Clostridium difficile, EHEC and sent acute gastroenteritis that are usually caused by EIEC. Sometimes Aeromonas hydrophila and Ple- enteric pathogens which have a self-limited course siomonas shigelloides that have severe enough diarrhea and generally does not need antibiotics (except in may also produce bloody diarrhea.29 Entamoeba his- patients with extreme ages), for example Non-O1 tolytica infections commonly present as chronic diar- vibrios, Vibrio parahemolyticus, Aeromonas spp., Ple- rhea, but they may sometimes present as acute bloody siomonas spp., Edwardsiella spp., Salmonella spp. It may also include the milder and uncomplicated forms of Bloody diarrhea is often accompanied by fever that diarrhea from Vibrio cholerae, Vibrio O139, Shigella may persist for longer than 2 days and may be higher boydii, Shigella sonnei, Campylobacter spp., Yersinia spp., than 38.5°C. Initially, these patients may pass watery and all groups of Escherichia coli.
stools that rapidly progresses to bloody diarrhea and In general, diarrhea is characterized by the passage of dysentery. Dysentery is characterized by the frequent loose or loose watery stools with some food residue in passage (usually 10–30 times a day) of small-volume the feces. These patients normally pass 4–8 stools a day stools consisting of blood, mucus and pus; this diarrhea without or with minimal signs of dehydration. There is accompanied by abdominal cramps and tenesmus, should be no gross blood or bloody mucoid material in the painful straining at stool that may lead to rectal the stool. Fever could be present but is often mild and prolapse. Diagnosis is enhanced if microscopically RBC does not last longer than two days. Abdominal pain and and WBC are found in the stool.27,30 It is essential to vomiting may be severe in the first few days but grad- exclude amoebic colitis by examining fresh stool for ually subsides in the following days. Abdominal tender- trophozoites. Seizures are rare in adults with bloody ness should be absent, both to light and deep palpation.
diarrhea. Mild dehydration is common and severe dehy- If stool microscopic examination is available, it charac- dration is very rare. The hemolytic uremic syndrome teristically shows no ova or parasites, RBC or WBC.
rarely complicates bloody diarrhea. Bacteremia is asso- However, small numbers of RBC and WBC are some- ciated with higher-than-usual mortality and is more times present microscopically, but do not exceed 20 common among elderly patients31–33 (see Appendix).
Treatment: The mild dehydration in bloody diarrhea
uals, the diarrhea will probably subside before the can be readily corrected with ORT and intravenous culture results become available.38,39 Stool culture is therapy is often not needed. The use of antibiotics in advisable in patients with bloody diarrhea, moderate to most patients with bloody diarrhea reduces the dura- severe diarrhea with objective evidence of dehydration, tion of illness and can shorten the carrier stage. For and those with diarrhea that does not subside after a practical purpose, after having excluded amoebic colitis few days.40 In the situation of an outbreak, nosocomial and EHEC or STEC by careful stool examination, it is diarrhea, or the specific conditions of acute diarrhea acceptable to start empiric therapy with antibiotics listed in Table 2, extensive work up with stool culture rather than waiting for stool culture results. If the local should be encouraged (see Appendix).
antibiogram of Shigella spp. is known, the preferred ‘Routine’ culture techniques vary from country to antibiotics can be selected. But if no information is country and hospital to hospital, depending on the available, one of the fluoroquinolones is preferred. Nor- availability, feasibility and local practice. When diarrhea floxacin 800 mg/day, ciprofloxacin 1000 mg/day or lev- is non-specific or indeterminate and there are limita- ofloxacin 500 mg/day for 3–5 days should be adequate tions of resources and facilities, routine stool culture for healthy adults. For geriatric patients, or septicemic with MacConkey agar is the minimal requirement.
prone conditions, ofloxacin or ciprofloxacin is pre- Because most laboratories in the USA do not culture ferred. It is imperative not to administer antimotility routinely for Vibrio cholerae or other Vibrio spp., clini- agents, such as loperamide, diphenoxylate, atropine and cians should request appropriate cultures for clinically codeine, as the drugs are suspected of enhancing the suspected cases.When cholera is suspected from a posi- severity of disease by delaying excretion of organisms tive DFM or presence of shooting bacteria from and thus facilitating further invasion of the mucosa.
light microscopy, thiosulfate-citrate-bile-salt-sucrose(TCBS) agar should be added to the routine Mac-Conkey agar to detect Vibrio group organisms. Further Stool examination
identification for Vibrio cholerae serogrouping should be done, together with the identi- Although fresh stool examination under light fications of Vibrio O139, Non-O1 Vibrio cholerae microscopy should be encouraged in every case,34 it and Vibrio parahemolyticus. When bloody diarrhea is may not always be practicable or possible. In real life suspected, selective media for Shigella, for example situations, assessment of patients with acute diarrhea salmonella-shigella agar or XLD agar should be added may have to rely solely on history and physical exami- to the routine MacConkey agar. Micro-aerophilic cul- nation. Hence, in the algorithm, stool examination is tivation technique with inhibitory media to detect recommended in patients with watery diarrhea with Campylobacter and special media for Yersinia should be dehydration and in patients with bloody diarrhea, but added to the routine culture.41,42 If traveler’s diarrhea is not considered as essential in patients with watery diar- diagnosed, culture for all bacterial causes should be per- rhea without dehydration. Depending on the avail- formed. For suspected EHEC associated diarrhea, Sor- ability, feasibility and local practice, stool examination bitol-MacConkey agar should be added to the routine may be done early in some cases and when it is done, culture.43 For antibiotic-associated enterocolitis, detec- the detection of microscopic RBC and WBC > 20 tion of C difficile Toxin A and B using ELISA or tissue cells/HPF by early stool examination may have some culture assay should be done (see Appendix).
predictive value in detecting early cases of bloody Fresh stool specimens should always be used when diarrhea. In patients with gross bloody diarrhea, stool possible to ensure that fastidious organisms that decom- examination can provide essential information for pose easily are detected before they degenerate. Stool differentiating shigellosis from amebiasis.35 In addition, specimens should be transported to the microbiology dark-field microscopy (DFM) is strongly recommended department ideally within 2 h after the passage, but in all patients with watery diarrhea with dehydra- 8–12 h would also be acceptable.44 In cases in which tion.36,37 A positive DFM for shooting bacteria should stool specimens are not available, rectal swabs should indicate the high possibility of Vibrio spp., especially be obtained and put in transport media until culture.
Vibrio cholerae, and appropriate antibiotics to eradicateVibrio cholerae should be promptly initiated. In situa-tions in which DFM is not available, fine adjustment oflight microscopic examination to look for active motile Unresolved diarrhea
‘shooting’ bacteria can be a helpful alternative to diag-nose Vibrio spp. as a cause of diarrhea. Presence of stool All patients who do not improve after rehydration, with ova and parasites in the stool should lead to appropri- or without antidiarrheals and/or empiric antibiotics, should require re-evaluation after 3–5 days, dependingon the severity of the continuing illness. Such patientsshould be informed to bring along his or her ‘fresh’ stool Stool culture
specimen for microscopic re-examination and/or re-culture at their next visit. They should be advised to In general, stool culture is probably not necessary in observe their stool. They should also be advised to patients who present to physicians with mild diarrhea consult their physician for re-evaluation if the stool without obvious signs of dehydration, and within the character changes and becomes more watery or bloody, first few days of onset of illness. In most such individ- if they develop high fever (> 38.5°C), if their stage of clinical dehydration does not improve, or if their as possible. Selection of antibiotics for corresponding abdominal pain becomes more intense or persistent.
enteropathogens should follow the antibacterial sensi- When the patient comes for the second visit, stool tivity of the pathogen that was isolated. In situations examination and culture should be done especially if where an antibiogram is not available, antibiotics selec- they were not performed in the first visit. In cases of tion should follow the available local or regional data bloody diarrhea without an identifiable pathogen, which regarding antibiotic susceptibility in that region or do not improve after empiric treatment, further country. If no such information is available, the use of investigation by doing sigmoidoscopy or colonoscopy conventional recommended antibiotics (as shown in together with biopsy is usually necessary.
Table 5) is recommended. It must be noted that anti-biotics are not recommended for some entero-pathogens, as there is no information to confirm the Sigmoidoscopy/colonoscopy
efficacy of antibiotic use or the available informationsuggests that antibiotic use in this particular situation Patients who were managed along the scheme of the may actually be deleterious. Again, it should be stressed algorithm or have bloody diarrhea in spite of empiric that dehydration needs to be properly corrected in all antibiotics, and did not improve, should be further cases, no matter the result of the stool culture.
investigated by sigmoidoscopy or colonoscopy. Colonicbiopsy together with culture should be performed eventhough the mucosa may look normal endoscopically.45 Oral rehydration
Selective antibiotics for known pathogens
In this article, the term ORS (Oral Rehydration SaltsSolution) and ORT (Oral Rehydration Therapy) are Whenever stool examination and culture results are used.To avoid confusion, clarification of these terms are available, treatment should be as selective and specific Recommended antibiotics against specific enteric pathogens Doxycycline, 300 mg single doseTMP-SMZ, 160–800 mg b.i.d. ¥ 3 dFluoroquinolone* ¥ 3 d Doxycycline, 300 mg single doseTMP-SMZ, 160–800 mg b.i.d. ¥ 3 dFluoroquinolone* ¥ 3 d Antibiotics are usually not required, except in Antibiotics are usually not required, except in Gentamicin#, 80 mg ¥ 5–7 dCefotaxime#, 1 g q.i.d. ¥ 5–7 d Ceftriaxone#, 1 g b.i.d. ¥ 5–7 dAzithromycin 250 mg single dose Antibiotics are usually not required, except in Antibiotics are usually not required, except in Antibiotics are usually not required, except in Antibiotics are usually not required, but may be Fluoroquinolone* ¥ 3 dTMP-SMZ, 160–800 mg b.i.d. ¥ 3 d Antibiotics have no established therapeutic value and are usually not required, except in Antibiograms are needed. (Mostly in children) Antibiotics are usually not required, except in Enteroaggregative 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 Antibiotics are usually not required, except in Offending antibiotics should be withdrawn if Vancomycin 125–250 mg q.i.d. ¥ 10-14 d Metronidazole, 250–500 mg q.i.d. ¥ 10–14 d aantibiotics may be required in septicemic prone conditions e.g. cirrhosis, or immunocompromised hostsbantibiotics may be required in severely ill patients, or traveler’s diarrhea, or septicemic prone conditions e.g. cirrhosis, uncon- trolled diabetes mellitus, or immunocompromised hosts cantibiotics may be required in severely ill patients, or age < 6 months or > 65 year old, or immunocompromised hosts, or sep- ticemic prone conditions e.g. patients with prosthesis, valvular heart disease, or severe atherosclerosis, or malignancy, or uremia,or uncontrolled diabetes mellitus.
dantibiotics may be required in severely ill patients, or immunocompromised hostseantibiotics may be required in severely ill patients, traveler’s diarrhea, or immunocompromised hosts, or septicemic prone conditions, or uncontrolled diabetes mellitus.
fantibiotics may be required in severely ill patients, traveler’s diarrheagantibiotics may be required in severely ill patients, or associated bacteremia, or when bacteremia is suspected, or immuno- *fluoroquinolone, for example 300 mg ofloxacin, 400 mg norfloxacin, or 500 mg ciprofloxacin b.i.d.
#antibiotics for suspected septicemic cases Oral rehydration salts solution (ORS) also refers to non-ORS measures of rehydration, includ- Oral rehydration salts solution refers to the oral rehy- ing various natural or formulated electrolyte containing dration salts formula that is recommended by WHO. It contains sodium chloride 3.5 g, sucrose 40 g (or glucose Adult patients with watery diarrhea and clinical dehy- 20 g), trisodium citrate dihydrate 2.9 g (or sodium dration should receive the proper WHO-recommended bicarbonate 2.5 g) and potassium chloride 1.5 g in one ORS formula to correct their dehydration, especially in litre of clean drinking water. This combination should endemic areas of cholera. In other parts of the world give the concentration of sodium 90 mEq/L, potassium 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 ORSformula in conjunction with intermittent free waterdrinking. In adults, the chance of having hyponatremia or hypernatremia may be much greater in the elderly.31 Oral rehydration therapy in the context of these guide- Hence, ORT or usage of lower sodium concentration of lines refers to the use of informal oral rehydration ORS, may be more appropriate in elderly patients. In formulas or electrolyte packages with lower sodium geriatric patients, periodic assessment of serum elec- concentration than the one recommended by WHO. It trolytes may be necessary. The super ORS, which contain glycine or starch (cereal-based formulations) oping world, where diarrhea is very prominent. In are receiving increased attention.51 Because of their industrialized countries, the antidiarrheal compounds lower osmolarity, they may reduce stool output and may be cost effective and useful in returning people better enhance electrolytes absorption. The use of resis- more quickly to work and school during a bout of tant starch to provide colonic short chain fatty acids There is a wide variety of antidiarrheal drugs avail- In general, ORS or ORT should be taken by mouth able on the market. Physicians in each region of the slowly and intermittently by ‘sipping’ little by little, not world will have to keep in mind the cost-risk-benefit ‘drinking’ in large amount in a short period of time.The ratios and make their own judgment in selecting or amount to be taken should be approximately 1.5–2 recommending the antidiarrheals. In the following times the estimated amount of deficit plus concurrent paragraphs the evidence supporting the use of each antidiarrheal drug is briefly reviewed, so that physicianscan decide which to use by judging from their efficacy,side-effects, indications and contra-indications basedon the available literature. Antidiarrheal drugs are Intravenous fluid replacement
grouped and discussed under the following topics.
For initial management of severely dehydrated or hypo-volemic shock patients, immediate intravenous fluid Antiperistaltics or antimotility drugs replacement is essential. Patients with moderate ormilder degree of dehydration may also need intravenous Most available antiperistalic agents act by altering fluid replacement if they have severe vomiting and are intestinal motility. Some also may have mild pro- unable to drink ORS properly. Patients with dull con- absorptive or antisecretory activity. They include sciousness, who may harbor the risk of aspiration, loperamide, diphenoxylate, codeine, tincture opium and should also be rehydrated intravenously. Ringer’s lactate other opiates. They may be helpful in secretory diarrhea is best recommended for all forms of acute diarrhea in of mild to moderate severity by reducing the frequency adults, as it contains potassium 4 mEq/L, which can and volume of stools.53–55 Among all antimotility drugs, be replaced rapidly in large amounts according to the loperamide is the most commonly recommended agent severity of deficit. The total fluid deficit in severely for use in uncomplicated diarrhea.28,56 However, such dehydrated patients can be replaced safely within the antimotility agents are contraindicated in diarrhea first 4 h of therapy, half within the first hour.52 The caused by invasive pathogens because the induced volume of fluid to be administered is determined by the intestinal stasis may enhance tissue invasion by the rate of stool losses and the degree of pre-existing dehy- organisms or delay their clearance from the bowel.
dration. Meanwhile, oral therapy usually can be initi- Hence, bloody diarrhea with high fever, immunocom- ated with the goal of maintaining fluid intake equal to promised host and septicemic prone conditions with the ongoing loss. However, patients with continued diarrhea should not be given this group of drugs.
large-volume diarrhea might require prolonged intra- Some of these drugs may cause addiction, if they are venous treatment to keep up with gastrointestinal fluid to be administered for a long period. Suppression of res- losses. It should also be used with additional potassium piration is significant in children and may be harmful supplements by mouth. The oral route of rehydration in elderly people with chronic lung disease. The newer and potassium replacement is safer than the intravenous loperamide preparation, loperamide oxide, may be the route and is physiologically regulated by thirst and urine drug in this group with the least side-effects.57 Response to loperamide can vary from one person to another.Theaim should be to reduce the frequency of diarrhea, notto ‘stop’ diarrhea.
Antidiarrheal drugs
While every effort should be made to identify andcorrect the specific causes of diarrhea, in many cases, They include atropine, hyoscine, hyoscyamine and dicy- causes that are specific and potentially treatable are clomine. They are not effective in reducing the fre- often not identifiable. Identification is not possible and quency and volume of stools, but may have some value symptomatic therapy alone is commonly indicated.
in selected cases in reducing pain from abdominal Although most diarrheas are self-limited, some cramps.58 High dose of anticholinergics may cause dry antidiarrheal drugs may help in reducing amount of mouth, urinary retention, blurred vision, palpitation, fluid loss, frequency and consistency of stool, or shorten the clinical course of diarrhea. The addition of antidiar-rheal drugs improves the quality of life to a certainextent at the financial cost of the drugs.The cost-benefit ratio of using various antidiarrheal agents has not There are a variety of drugs in this group, for example been properly studied. As acute diarrhea is a very activated charcoal, kaolin, pectin, dioctahedral smectite, common condition affecting large numbers of people, attapulgite (anhydrous aluminum silicate), aluminum the routine usage of antidiarrheals could mean a great hydroxide and tannic acid. Theoretically these medica- financial burden to countries, especially in the devel- tions adsorb toxins produced by toxigenic bacteria and act by preventing their adherence to intestinal mem- controlling motility and secretion of the gut. As 5HT branes. To be effective, they have to be given very early is also a neurotransmitter found in the brain and before the toxins are fixed to intestinal mucosa. Their the enteric nervous system (ENS). The antagonists of efficacy depends on their potency to adsorb toxins, 5HT3 receptor were found to inhibit extrinsic sensory some preparations, for example dioctahedral smectite, neuron stimulation (which can inhibit nausea, vomit- attapulgite and bismuth preparations are more effective ing, stomach pain and bloating) and reduce peristalsis in adsorbing toxins than others.59–61 In clinical trials, and secretory reflex. As a result, they help to reduce they can increase stool consistency and decrease stool stool volume and improve stool consistency. Another frequency, but cannot reduce the amount of fluid loss.
newer antisecretory agent is oral enkephalinase They only mask its extent and dehydration is not pre- inhibitor (Racecadotril). It prevents the degradation of vented.When prescribing these medications, it is impor- endogenous opioids (enkephalins), thereby reducing tant to maintain adequate hydration and proper diet, hypersecretion of water and electrolytes into the intesti- especially in the elderly. Adsorbents are not effective in nal lumen. Clinical trials that show the efficacy of these patients with febrile bloody diarrhea. In rare instances, drugs in the management of acute diarrhea in children they may cause constipation. Prolonged use may inter- and adults are being validated.73,74 Octreotide, which is fere with some medications, for example theophylline a long-acting synthetic analog of somatostatin, has a sig- and digoxin. Psyllium and other hydrophilic agents are nificant antisecretory effect.75 It is expensive and has to bulk forming agents, which absorb water and thereby be administered subcutaneously. It is more reasonable enhance stool consistency. Commonly, they are used in to prescribe in otherwise refractory cases of chronic chronic diarrhea and irritable bowel syndrome, not in There are an enormous numbers of herbal medicines Probiotics are non-pathogenic organisms, for example around the world that are claimed to be effective in Lactobacillus acidophilus and Saccharomyces boulardii, treating diarrhea. However, there is very little scientific which multiply in the patient’s intestine and produce data to support or confirm the efficacy of these medi- metabolites, which increase acidity of stool and prohibit cines, or if results are available, they are mostly incon- the growth of enteropathogens. They prevent the inva- clusive and anecdotal. However, they are cheap and sion of bacteria in intestine tissue, and produce short locally available. Administration of herbal medicine that chain fatty acids that are beneficial for intestine recov- is shown to be harmless in mild watery diarrhea without ery, and increase the rate of fluid and electrolyte absorp- dehydration can be locally accepted, provided that the tion. In children, there are studies which show that the dehydration is properly corrected and patients with use of probiotics could reduce the clinical course of febrile dysentery are properly managed. Herbal medi- acute diarrhea.62–64 In adults, they are used mainly in cines should not be recommended in severe diarrhea no chronic diarrhea and relapse of antibiotic associated CONCLUSION
There are many drugs in everyday use that have anti-secretory effects in vitro, for example phenothiazine, Acute diarrhea in adults is a common every-day condi- chlorpromazine, aspirin, indomethacin, lithium car- tion all over the world. Besides acute infectious diar- bonate, and calmodulin-inhibitors. They work by a rhea, the definition also encompasses many intestinal variety of different mechanisms including inhibition of conditions that may present as acute diarrhea. Stool prostaglandins and effects on cyclic AMP, calmodulin examination and culture results are often not available, inhibition,66 inhibition of gut hormones and encephali- and proper hydration together with empiric treatment nase inhibition of chloride channels.67 But some of these has to be initiated. A practical approach for the man- drugs have to be administered in very high doses to give agement of adult patients with acute diarrhea is pre- effective antisecretory effects in vivo. Hence, their drug- sented in an algorithmic diagram. After careful history related side-effects preclude them from being used taking and a physical examination to exclude other con- effectively.68,69 This group of drugs is more physiologic ditions that may present as acute diarrhea, and other in approach and may become the ideal agents for use specific situations of acute diarrhea that deserve to be in acute diarrhea. Bismuth salts preparations, according approached differently, patients are classified as having to their mode of action, are also an antisecretory agents.
predominately diarrhea or predominately vomiting.The They are found to be as effective as loperamide, and diarrhea predominant group is further classified into reduce the number of stools passed by about 50%, with watery diarrhea and bloody diarrhea subgroups by their improvement in other associated symptomatology.70,71 gross stool appearance. The watery diarrhea subgroup The untoward side-effects of bismuth preparations are with clinical dehydration will have to exclude cholera by blackened stool, blackened tongue, tinnitus and fecal stool examination with dark field microscopy confirmed later by stool culture. The watery diarrhea without clin- Recently, drugs that affect 5-hydroxytryptamine ical dehydration subgroup is managed by ORT with or (5HT) or serotonin were found to have a pivotal role in without antidiarrheals.The bloody diarrhea subgroup is treated with antibiotics either empirically or after stool 15 Stenhoff MC, Douglas RGJ, Greenberg HB, Callahan examination and culture to rule out EHEC or STEC.
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87 Carter AO, Borczyk AA, Carlson JA et al. A severe out- 103 Khuri-Bulos NAAK, Shehabi A, Shami K. Foodhandler- break of Escherichia coli 0157: H7–associated hemor- associated Salmonella outbreak in a University hospital rhagic colitis in a nursing home. N. Engl. J Med. 1987; despite routine surveillance cultures of kitchen employ- 317: 1496–500.
ees. Infect. Control Hops. Epidemiol. 1994; 15: 311–4.
104 Reves RRMA, Bartlett AV et al. Child day care increases 122 Bircks W, Reidemeister C, Sadony V, Schulte HD, Tarbiat the risk of clinic vistis for acute diarrhoea and diarrhoea S. Diagnostic and therapeutic problems of septicemia due to rotavirus. Am. J. Epidemiol. 1993; 137: 97–107.
after valvular replacement. J. Cardiovasc Surg. (Torino) 105 Bacillus cereus food poisoning associated with fried rice 1972; 13: 385–9.
at two child day care centers-Virginia 1993. MMWR 123 Aksnes J, Abdelnoor M, Berge V, Fjeld NB. Risk factors Morb. Mortal.Wkly Rep. 1994; 177–8.
of septicemia and perioperative myocardial infarction in 106 Emont SL, Cote TR, Dwyer DM, Horan JM. Gastroen- a cohort of patients supported with intra-aortic balloon teritis outbreak in a Maryland nursing home. Md Med. pump (IABP) in the course of open heart surgery. Eur. J. 1993; 42: 1099–103.
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107 Sims RV, Hauser RJ, Adewale AO et al. Acute gastroen- teritis 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 APPENDIX
the colon in graft-versus-host disease. Mod. Pathol. 1998;
11: 513–5.
The following specific conditions of acute diarrhea are 109 van Kraaij MG, Dekker AW,Verdonck LF et al. Infectious specifically mentioned here as there are theoretical basis gastro-enteritis. an uncommon cause of diarrhoea in and scientific information to warrant special consider- adult allogeneic and autologous stem cell transplant ations. They should be managed differently from the recipients. Bone Marrow Transplant 2000; 26: 299–
suggested algorithm in this report. These conditions 110 Yeomans A, Davitt M, Peters CA, Pastuszek C, Cobb S.
Efficacy of chlorhexidine gluconate use in the preventionof perirectal infections in patients with acute leukemia.
Acute diarrhea in the elderly
Oncol. Nurs. Forum 1991; 18: 1207–13.
111 Kraus A, Guerra-Bautista G, Alarcon-Segovia D. Salmo- Acute diarrhea that occurs in patients aged over 65 nella arizona arthritis and septicemia associated with years is associated with higher mortality.31,32,76 Diarrhea rattlesnake ingestion by patients with connective tissue is a common problem among the elderly that can have diseases. A dangerous complication of folk medicine. J. catastrophic results. Atherosclerosis predisposes older Rheumatol. 1991; 18: 1328–31.
adults to morbid sequelae from dehydration resulting 112 Poulos JE, Cancio M, Conrad P, Nord HJ, Altus P. Non from diarrhea. Ischemic colitis is a serious differential 0–1 Vibrio cholerae septicemia and culture negative neu- diagnosis especially in developed countries.77 Deaths trocytic ascites in a patient with chronic liver disease. J. related to diarrheal illnesses are recognized among older Fla. Med. Assoc. 1994; 81: 676–8.
adults living in the community as well as among those 113 Merlin M, Gandara S, Iannicillo H et al. Acute and confined to nursing homes. Outbreaks have most often chronic diarrhoea in AIDS. Study 435 (HIV+) Patients, been associated with excess deaths from diarrhea Buenos Aires. Acta Gastroenterol. Latinoam 1996; 26:
among nursing-home patients. Although most cases of dehydration from diarrhea result from gastrointestinal 114 Weber R., Ledergerber B, Zbinden R. et al. Enteric infec- infections, non-infectious causes of diarrhea related to tions and diarrhoea in human immunodeficiency virus- prescription of laxatives, side-effects of medications and infected persons: prospective community-based cohort use of enteral feedings are common. Clostridium difficile study. Swiss HIV Cohort Study. Arch. Intern. Med. 1999; infection is particularly common among older adults in 159: 1473–80.
hospitals and nursing homes, and relapsing disease in 115 Du Pont HL, Marshall GD. HIV-associated diarrhea and these groups may be more frequent than among wasting. Lancet 1995; 346: 352–6.
younger adults. The approach to an elderly patient with 116 Ramakrishna BS. Prevalence of intestinal pathogens in diarrhea is to ensure proper hydration using available HIV patients with diarrhea: implications for treatment.
oral rehydration solutions, proceed with diagnostic tests Indian J. Pediatr. 1999; 66: 29–36.
likely to yield a positive result, avoid the use of harmful 117 Levine GI. Sexually transmitted parasitic diseases. Prim. antiperistaltic drugs, and provide adequate follow-up of Care 1991; 18: 101–28.
the nutritional state. Antibiotics should be administered 118 Gagarin VV. Acute disorders of the mesenteric circula- in acute diarrhea due to invasive bacteria, especially tion among heart defect patients. Kardiologiia 1984; 24:
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; Traveler’s diarrhea
25: 215–16.
120 Christenson B, Soler M, Nieves L, Souchet LM. Sep- This is a specific entity that occurs after a person has ticemia due to a non-0: 1, non-0: 139 Vibrio cholerae.
traveled from an industrialized country to a developing Bol. Asoc. Med. P. R. 1997; 89: 31–2.
country and experienced acute diarrhea. The risk 121 Chan HL, Ho HC, Kuo TT. Cutaneous manifestations increases if the traveler consumes food from street of non-01 Vibrio cholerae septicemia with gastroenteritis vendors rather than from a restaurant or a hotel. Symp- and meningitis. J. Am. Acad. Dermatol. 1994; 30: 626–
toms and severity depend on the prevalence of common pathogens endemic in the developing country.
The common causes of acute traveler’s diarrhea vary tissue culture assay technique in confirming diagnosis.
from one geographical area to another.78–84 The most Sigmoidoscopy or colonoscopy may reveal normal, frequently identified pathogen causing traveler’s diar- minimally erythematous colonic mucosa with some rhea is toxigenic Escherichia coli, although in some parts edema, or granular, friable, or hemorrhagic mucosa of the world (notably North Africa and South-east with typical pseudomembrane formation.
Asia), Campylobacter infections appear to predominate.
The course is highly variable. In patients with clini- Other common causative organisms include enteroag- cally mild disease, withdrawal of offending antibiotics gregative E. coli, Salmonella spp., Shigella spp., rotavirus usually leads to prompt resolution of symptoms. Those and the Norwalk agent. Except for giardiasis, cryp- who have more protracted diarrhea usually need spe- tosporidium and cyclosporidium, parasitic infections cific therapy. Oral rehdyration therapy is the mainstay are uncommon causes of traveler’s diarrhea.
treatment to correct dehydration. Intravenous fluid may The disease is usually short-lived, self-limited, be required in severe cases. Empiric metronidazole however, many of them are amenable to antibiotics.
250–500 mg four times daily should be administered Choice of antibiotics depends on epidemiologic data.
while waiting for the result of a cytotoxin study, The same principle should apply in correcting dehy- and should be continue for 10–14 days. If cytotoxin dration from other types of diarrhea. Antidiarrheal study is positive and the patient does not get better drugs can be given in conjunction with antibiotics.
after a week of metronidazole, then vancomycin A growing problem for travelers is the development 125–250 mg/day should be substituted. Relapses or of antibiotic resistance in many bacterial pathogens; reinfections are common and occur in as many as 20% examples include strains of Campylobacter resistant of cases. These patients can be treated with the same to quinolones and strains of E. coli, Shigella, and Sal- treatment as given for the primary infection. Subse- monella resistant to trimethoprim-sulfamethoxazole.
quent recurrences of antibiotic associated enterocolitisare best managed with vancomycin plus rifampicin.
Antidiarrheal drugs have no advantage in treatingantibiotic-associated enterocolitis, except cholestyra- Antibiotic associated enterocolitis
mine and probiotics, which can be helpful in chronic orrelapsing disease.
Diarrhoea that occurs as a result of administered anti-biotics which alter the normal intestinal flora andincrease the proliferation of Clostridium difficile, produceenterotoxin A and B that cause enterocolitis and Hemorrhagic colitis (due to
Enterohaemorrhagic E. coli, EHEC or
antibiotics usage prior to the development of diarrhea Shiga Toxin Producing E. coli, STEC)
may raise the possibility of antibiotic associated entero-colitis, however, the use after the onset of diarrhea Hemorrhagic colitis, caused by enterohemorrhagic usually does not suggest antibiotic associated enter- Escherichia coli (EHEC), should always be a differential ocolitis. Onset of symptoms occurs either during anti- diagnosis in patients who present with acute bloody microbial administration or within four weeks after diarrhea, especially during an outbreak of food-borne treatment. While all antimicrobials may cause the syn- illness. Patients who present with non-bloody diarrhea drome, some drugs cause it more commonly than that progresses to bloody diarrhea should also raise the others and some only rarely. The common causes of possibility of EHEC diarrhea. Other prominent com- antibiotic associated enterocolitis include clindamycin, plaints include striking abdominal pain and tenderness ampicillin, and the cephalosporins. The rare causes of often in the absence of fever. In an outbreak situation, antibiotic associated enterocolitis are vancomycin, some patients with EHEC infection may be asympto- metronidazole, and the aminoglycosides.
matic and are only recognized during epidemiologic The clinical spectrum of antibiotics-associated ente- surveillance in association with symptomatic cases. In rocolitis is diverse. It ranges from mild loose watery general, the mortality rate is 1–2%,86 although it may diarrhea to severe colitis causing bloody or dysentery- be substantially higher in the young and the elderly.87 like diarrhea in the later course of the disease. In the The most worrisome complication of EHEC infection first week, diarrhea is usually watery, voluminous and is the hemolytic–uremic syndrome (HUS),88 which without gross blood or mucus. Later, it becomes bloody.
most frequently involves children between the ages of Other symptoms also vary considerably. At one end of 5–10 years.89 Hemolytic-uremic syndrome is character- the spectrum are many patients with annoying diarrhea ized by the triad of acute renal failure, microangiopathic with no severe systemic toxicity; while at the other end hemolytic anemia, and thrombocytopenia. Patients who are those with high and prolonged fever with abdomi- also have fever and neurologic symptoms are considered nal pain. Abdominal pain can be severe with cramping, to have the related disorder thrombotic thrombocy- especially at the left iliac fossa. Vomiting is uncommon topenic purpura (TTP), which has also been associated and dehydration is often mild except in very severe with E. coli O157:H7 infection.86,90 Hemolytic-uremic cases. Examination of stool may reveal large numbers syndrome usually begins 5–10 days after the onset of of red blood cells and some leukocytes. Stool culture diarrhea.86,90,91 The incidence of subclinical renal dys- for C. difficile needs anaerobic conditions and may take function is substantially higher, particularly in patients several days to perform. It is usually more practical to with prolonged anuria during the initial presenta- perform cytotoxin assay in the stool using ELISA, or tion.92,93 Stool culture using sorbitol-MacConkey agar should be done in all suspected EHEC diarrhea. The In the situation in which there is a known outbreak Centers for Disease Control and Prevention (CDC) has of an epidemiologically important enteric pathogen, recommended that all stools from patients with a for example cholera, salmonella, shigella, campylobac- history of bloody diarrhea should be screened for E. coli ter, EHEC (STEC), any acute diarrheas that occur in O157:H7 or Shiga toxin by direct stool examination.92 the outbreak area should be managed as if they are E. coli strains presumptively identified as E. coli caused by the ‘outbreak pathogen’, no matter the sever- O157:H7 and Shiga toxin-positive stools should be sent ity of diarrhea. As in an outbreak situation, the disease to a reference laboratory for confirmation. A number of spectrum is often highly variable, ranging from very newer diagnostic approaches for EHEC infection mild to very severe. All acute diarrhea in the outbreak focuses on direct detection of Shiga toxins in stool, or area should be reported to the Area Health Authority the use of DNA probes for detecting the toxin genes in and proper epidemiologic investigation should be fecal isolates. One such assay, the Premier EHEC assay, employed. Rapid testing or a kit that is helpful in iden- utilizes an enzyme-linked immunosorbent assay tifying the ‘outbreak pathogen’ should be used in the (ELISA) to detect both Shiga toxin 1 and Shiga toxin field and further confirmation can be done later in a reference center. Antibiotics that are known to be The only current treatment of EHEC infection is effective in eradicating the pathogen should be empiri- supportive, with monitoring for the development of cally administered to all acute diarrhea cases in the out- microangiopathic complications such as HUS. The break area. The purpose is to contain the spreading impact of antibiotic therapy on the duration of diarrhea of the disease, not necessarily to shorten the clinical or on the subsequent occurrence of systemic complica- course of diarrhea in that particular case. Epidemiologic tions is controversial. The use of antibiotics may actu- surveillance is necessary until the outbreak completely ally increase the risk of HUS, perhaps by increasing production or release of toxin.94 A number of newapproaches to therapy of EHEC infection are currentlybeing evaluated, but are not yet proven effective nor Institutional diarrhea
residues given orally and hyperimmune antitoxin This is acute diarrhea that occurs in persons who stay in an institution where there is a uniform populationwith the same clinical or social setting, for example anursing home, a day-care center, a refugee camp, Nosocomial diarrhea
Any single case of acute diarrhea that occurs in an Nosocomial diarrhea, that is acute diarrhea that occurs institution should all be investigated by stool examina- in hospitalized patients, is an important problem in hos- tion and culture, as there is risk of spreading among pitals, and in critical care units in particular. Hospital- inhabitants in the same institution and may progress to acquired diarrhea may be on an infectious or an established outbreak of diarrhea. Apart from the non-infectious basis. Common non-infectious causes of routine correction of dehydration, there should also be nosocomial diarrhea include food intolerance, drug isolation of the patient and an improvement of hygiene induced diarrhea, drug-induced changes in the fecal and sanitation in the institution. Early empiric treat- flora, or changes secondary to enteral hyperalimenta- ment with antibiotics may help to contain the suspected tion.95,96 Infectious causes of nosocomial diarrhea are enteropathogens. In patients with diarrhea due to sal- due to eating food contaminated with enteric pathogens monella, empiric antibiotic treatment may increase the or in outbreak situations. However, the major cause time of shedding of the organism by one to three weeks.
of sporadic (non-epidemic) nosocomial diarrhea is Antibiotics are usually not given to otherwise healthy Clostridium difficile.96 All cases of nosocomial diarrhea patients with milder forms of non-typhoid salmonel- should be properly investigated with stool examination, losis. The young or the elderly and patients with culture and C. difficile cytotoxin assay.97,98 Proper hydra- immunocompromised are usually given antimicrobials tion together with dietary adjustment should immedi- in intestinal salmonellosis. In confirmed groups, other ately be employed. If possible, discontinuation of organisms may produce illness in individuals or as out- offending drugs or antibiotics should be considered.
breaks. The cause of the illness generally requires labo- Empiric metronidazole can be started in patients with a possibility of antibiotic associated enterocolitis. (Seeantibiotic associated enterocolitis for details of thisinfection). Systemic antibiotics may be necessary in Acute diarrhea in immunocompromised
patients
Acute diarrhea that occurs in an immunocompromised Outbreak diarrhea
host, who has been treated with immunosuppressiveagents or chemotherapy, or those with HIV infection, Acute diarrhea that occurs in two or more persons from autoimmune diseases, malignancy, especially hemato- the same exposure, assumed to be caused by the same logic malignancy, and acute graft-versus-host condition pathogens, is considered an outbreak.99–103 are a special entity.108,109 Acute diarrhea that occurs in these patients may easily lead to septicemia, hence early including parasitic protozoans and helminths. The most antibiotic therapy during their course of diarrhea common of these parasitic infections are amebiasis, should be instituted, no matter the type or severity of caused by Entamoeba histolytica, and giardiasis caused the diarrhea.110–112 Apart from the hemodynamic by Giardia lamblia.117 Both entities may cause acute or support, parenteral antibiotics are often needed. Bloody chronic diarrhea, as well as other abdominal symptoms.
diarrhea in immunocompromised patients may also be Most gay men with amebiasis are asymptomatic, and caused by cytomegalovirus enteric infection.
invasive disease in this group is extremely rare. Both Acute and chronic diarrhea that occurs in an HIV amebiasis and giardiasis can be diagnosed on the infected person should receive special attention in terms basis of microscopic examination of stool specimens, of investigation and management.113,114 HIV infected although duodenal aspiration is occasionally necessary persons, who are not yet immunocompromised or to confirm a diagnosis of giardiasis. Metronidazole is having CD4 count > 500 cell/mm3, can be managed as efficacious in the treatment of both amoebiasis and gia- in the suggested algorithm (Fig. 1). But HIV infected rdiasis. Other common causes of diarrhea in homosex- persons who are immunocompromised or their CD4 ual males include the spread of the organisms by counts are < 500 cell/mm3, apart from doing routine the fecal oral route (e.g. shigella, campylobacter, stool culture and examination, stool staining for AFB, salmonella) and those spread by receptive anal inter- modified AFB, modified trichrome staining and C. course (e.g. Neisseria gonorrhoeae, Chlamydia trachoma- difficile cytotoxin assay should also be employed.
tis, Herpes simplex and Treponema pallidium.) Blood cultures should be performed since entero-pathogens and Mycobacterium-avium intracellulareoften produce bacteremia in immunocompromisedpatients.115 Empiric treatment can be considered if the Acute diarrhea in septicemic
nature of enteropathogens infecting these patients is prone conditions
known.116 Specific treatment with antibiotics, if beingadministered, should be given in a more prolonged Acute diarrhea that occurs in a person who is prone to course to ensure the complete eradication of the septicemia due to the presence of some underlying con- pathogen and prevent early relapse. Nutritional man- ditions that are not truly immunocompromised condi- agement is also required in this group of patients.
tions but were reported to have related higher incidenceof septicemia with diarrhea, or complications whendiarrhea occurs, for example cirrhosis, especially alco- Gay bowel syndrome
holic cirrhosis, uncontrolled diabetes mellitus, patientswith heart valves, prosthesis, severe atherosclerosis with This is a specific syndrome of acute diarrhea that occurs aortic aneurysm, malignancy and uremia.118 in homosexual men who may or may not be infected There are several reports of-Non-O1 Vibrios sep- with HIV. Homosexual people are a unique group of ticemia in patients with cirrhosis.47,119,120 Uncontrolled patients who are prone to diarrhea due to their sexual diabetes mellitus patients with diarrhea are prone to activity, which is the primary method of transmission gram negative septicemia.121 Patients with heart valve, for several important enteric parasitic diseases. The prosthesis, severe atherorosclerosis are prone to salmo- majority of parasitic sexually transmitted diseases nella septicemia and lodging of salmonella infection at involve protozoan pathogens; however, nematode and the diseased heart valve and prosthesis.122,123 These arthropod illnesses are also included in this group. Oral- patients should be aware of the possibility of septicemia anal and oral-genital sexual practices predispose male and an early empiric parenteral antibiotic should be homosexuals to infection with many enteric pathogens, administered from the first presentation.

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