Travelers\' diarrhea_ Clinical manifestations, diagnosis, and treatment - UpToDate
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29/09/2019
Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment - UpToDate
Official reprint from UpToDate® www.uptodate.com ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment Authors: Regina LaRocque, MD, MPH, Jason B Harris, MD, MPH Section Editor: Stephen B Calderwood, MD Deputy Editor: Allyson Bloom, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Aug 2019. | This topic last updated: Dec 03, 2018.
INTRODUCTION Travelers' diarrhea is the most common illness in persons traveling from resource-rich to resourcelimited regions of the world [1,2]. Among travelers to such areas, 40 to 60 percent develop diarrhea [3]. Episodes of travelers' diarrhea are nearly always benign and self-limited, but symptoms may disrupt planned activities and result in health care visits for some travelers [4]. There is a growing recognition that travelers' diarrhea and its self-treatment abroad are associated with the acquisition of organisms harboring antibiotic resistance [5-8]. The clinical features, diagnosis and evaluation, and treatment of travelers' diarrhea are discussed here. The microbiology, epidemiology, and prevention of travelers' diarrhea are discussed elsewhere. (See "Travelers' diarrhea: Microbiology, epidemiology, and prevention".)
DEFINITIONS Travelers' diarrhea refers to diarrhea that develops in individuals from resource-rich settings during or within 10 days of returning from travel to resource-limited countries or regions. Clinically, the severity of travelers' diarrhea can be categorized according to a classification scheme suggested by an expert panel of the International Society of Travel Medicine, which uses functional impact to define severity [9]: ●
Mild – Diarrhea that is tolerable, is not distressing, and does not interfere with planned activities
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Moderate – Diarrhea that is distressing or interferes with planned activities
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Severe – Diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools) is considered severe
For epidemiologic purposes, travelers' diarrhea has frequently been categorized into three forms: classic, moderate, and mild. These forms of travelers' diarrhea are defined as follows [10]: ●
Classic – Passage of three or more unformed stools in a 24 hour period plus at least one of these other symptoms: nausea, vomiting, abdominal pain or cramps, fever, blood in stools
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Moderate – Passage of one or two unformed stools in 24 hours plus at least one of the above symptoms or more than two unformed stools in 24 hours without other symptoms
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Mild – Passage of one or two unformed stools in 24 hours without other symptoms
These definitions allow some uniformity in studies of the epidemiology and etiologies of travelers' diarrhea. For such studies, the three types can be grouped together to estimate a total number of cases of travelers' diarrhea. (See "Evaluation of fever in the returning traveler".)
CLINICAL MANIFESTATIONS Classic symptoms — The symptoms of travelers' diarrhea depend upon the microbial etiology. The classic "turista" due to enterotoxigenic Escherichia coli (ETEC) generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. Very frequent stools are uncommon. Nausea and vomiting also may occur. Typically there are no symptoms of colitis such as blood or pus in the stool. Patients may develop a low grade fever. As an example, in a prospective study of 390 travelers from the Netherlands to subtropical and tropical regions, 160 (41 percent) reported travelers' diarrhea (defined as three or more unformed stools within a 24 hour period) on post-travel questionnaires [11]. Of those with diarrhea, 86 percent reported watery stools, 77 percent abdominal discomfort or cramps, and 71 percent fecal urgency. Twenty percent reported vomiting, and only 11 percent had a fever. Most had three to five stools per day; three percent had >10 stools per day. Ten percent reported only loose stools without accompanying symptoms. While it is common to be unable to proceed with planned activities, only a minority of patients report requiring bedrest for one to two days. In a series of 30,369 travelers to Jamaica, among whom the attack rate for travelers' diarrhea was 24 percent, incapacity was reported for a mean of 11.6 hours from the illness onset [12]. Symptoms associated with specific etiologies — Even when other bacterial agents such as Campylobacter jejuni and Shigella spp are implicated, the symptoms initially experienced by the traveler are generally similar to those seen with ETEC. However, infections with these organisms may progress to include symptoms of colitis, such as fever, tenesmus, urgency, cramping, and https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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bloody diarrhea. (See "Clinical manifestations, diagnosis, and treatment of Campylobacter infection" and "Shigella infection: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.) Belching and other upper intestinal symptoms are typical of giardiasis, while profuse watery diarrhea is characteristic of cholera, cryptosporidiosis, and Cyclospora cayetanensis infection. The symptoms of microsporidiosis may be more subtle with bloating and intermittent diarrhea. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis" and "Epidemiology, clinical manifestations, and diagnosis of cryptosporidiosis" and "Microsporidiosis" and "Cyclospora infection".) Timing — Most episodes of travelers' diarrhea occur between 4 and 14 days after arrival [12], but travelers' diarrhea can occur within a much shorter time frame if the concentration of bacteria ingested is sufficiently high. The illness is generally self-limited with symptoms lasting for approximately one to five days. However, 8 to 15 percent of patients experience symptoms for more than one week and as many as two percent for more than one month [13]. Long-term sequelae — Subsequent development of chronic gastrointestinal symptoms, and in particular irritable bowel syndrome, has been reported in a sizable minority of patients following travelers' diarrhea. Postinfectious irritable bowel syndrome is discussed in detail elsewhere. (See "Pathophysiology of irritable bowel syndrome", section on 'Postinfectious'.)
DIAGNOSIS AND EVALUATION The diagnosis of travelers' diarrhea is made in an individual who develops unformed stools during or shortly after returning from travel to a resource-limited setting. Travelers' diarrhea is typically self-diagnosed. For those who present to medical care after returning home with uncomplicated travelers' diarrhea, determination of the microbiologic agent is generally unnecessary [14]. Management of travelers' diarrhea is often symptomatic and initiated without regard to the specific offending agent. Furthermore, routine stool cultures are rarely informative since ETEC and enteroaggregative E. coli (EAEC) cannot be distinguished from nonpathogenic E. coli on stool culture, and viral agents would not be identified with stool cultures. Culture-independent diagnostic testing, such as antigen-based molecular assays, is available but not yet in routine clinical use; its application may be limited by the identification of multiple potential pathogens [15] and the lack of associated antibiotic sensitivity testing. However, certain features may warrant a specific microbiologic workup that could potentially lead to targeted treatment. (See "Approach to the adult with acute diarrhea in resource-rich settings" and "Approach to diarrhea in children in resource-rich countries".) https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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In patients with fever and symptoms of colitis (bloody or mucoid stools, abdominal cramping), a stool culture should be performed to evaluate for Campylobacter or Shigella spp. If available, stool can also be tested for enterohemorrhagic E. coli and Shiga toxin. (See "Clinical manifestations, diagnosis, and treatment of Campylobacter infection", section on 'Diagnosis' and "Shigella infection: Clinical manifestations and diagnosis", section on 'Diagnosis' and "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)
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In patients with predominantly upper gastrointestinal symptoms (eg, bloating, gas, nausea), stool examination for Giardia lamblia, Cyclospora, and Isospora should be undertaken. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Cyclospora infection", section on 'Diagnosis'.)
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Travelers who have taken antibiotics in the preceding 8 to 12 weeks are at risk for Clostridioides (formerly Clostridium) difficile diarrhea and should be tested for this pathogen. (See "Clostridioides (formerly Clostridium) difficile infection in adults: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
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In patients who appear systemically ill, blood cultures should be taken to evaluate for Salmonella species, including Salmonella typhi. (See "Nontyphoidal Salmonella bacteremia" and "Epidemiology, microbiology, clinical manifestations, and diagnosis of enteric (typhoid and paratyphoid) fever", section on 'Diagnosis'.)
Additional workup may be warranted in individuals who have persistent diarrhea beyond 10 to 14 days, including consideration of testing for intestinal parasitic infections [14]. (See 'Patients with persistent diarrhea' below.)
DIFFERENTIAL DIAGNOSIS Acute diarrhea in travelers from resource-limited settings is most frequently caused by gastrointestinal infection. Diarrhea may also occur in the context of systemic infections, such as influenza, HIV infection, dengue fever, and malaria. Other non-infectious food-poisoning syndromes, such as shellfish or mushroom poisoning can cause diarrhea. These other syndromes can be differentiated from simple travelers' diarrhea by the presence of other distinguishing clinical features or specific diagnostic testing. (See "Evaluation of fever in the returning traveler" and "Overview of shellfish and pufferfish poisoning", section on 'Diarrheic shellfish poisoning' and "Clinical manifestations and evaluation of mushroom poisoning", section on 'Acute gastroenteritis'.) Additionally, new medications may be a cause of acute diarrhea in travelers; comparing the timing of initiation with the onset of diarrhea can help evaluate for this noninfectious etiology of diarrhea. https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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MANAGEMENT Management of travelers' diarrhea depends on the severity of illness. Fluid replacement is an essential component of treatment for all cases of travelers' diarrhea. Most cases are self-limited and resolve on their own within three to five days of treatment with fluid replacement only. Antibiotics and antimotility agents, often used together, may be warranted in certain circumstances. Antimicrobial therapy shortens the disease duration to about one day and antimotility agents may limit symptoms to a period of hours. Antimicrobial choice depends, in part, on the region of travel. The benefit of antibiotics must be weighed against potential risks, including adverse effects and selection for resistant bacteria. These issues are discussed in the sections that follow. When to seek care — Travelers from resource rich settings who develop diarrhea while traveling to resource limited settings generally can treat themselves rather than seek medical advice while traveling. However, medical evaluation may be warranted in patients who develop high fever, abdominal pain, bloody diarrhea, or vomiting and for whom empiric antibiotics have not been of benefit. Otherwise, for most patients while traveling or after returning home, medical consultation is generally not warranted unless symptoms persist for 10 to 14 days. Fluid replacement — The primary and most important treatment of travelers' (or any other) diarrhea is fluid replacement, since the most significant complication of diarrhea is volume depletion [16,17]. The approach to fluid replacement depends on the severity of the diarrhea and volume depletion. Travelers can use the amount of urine passed as a general guide to their level of volume depletion. If they are urinating regularly, even if the color is dark yellow, the diarrhea and volume depletion are likely mild. If there is a paucity of urine and that small amount is dark yellow, the diarrhea and volume depletion are likely more severe. ●
Mild cases – Patients with mild diarrhea may combine alternating sips of fluids that contain salt and fluids that contain sugar to replete and maintain hydration. Broth, fruit juice, or similar fluids may be used. Pedialyte is frequently useful in children. For mild diarrhea, the use of fluids is the critical factor; the fluid need not be oral rehydration solution. One study showed no difference in outcome between treatment with oral rehydration solution plus loperamide versus generic fluids and loperamide [18].
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Severe cases – Severe diarrhea should be treated with oral rehydration solution (ORS); this replaces needed electrolytes in the appropriate concentrations. Packets of oral rehydration solution are available in the pharmacies of most countries and can be mixed with clean drinking water [19]. ORS should be used until the individual is urinating regularly. Alternatively, a similar solution can be made by adding 1/2 teaspoon of salt, 1/2 teaspoon of baking soda, and 4 tablespoons of sugar to one liter of water. The electrolyte concentrations of fluids used for sweat replacement (eg, Gatorade) are not equivalent. (See "Approach to the
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adult with acute diarrhea in resource-rich settings", section on 'Fluid repletion' and "Oral rehydration therapy", section on 'Clinical management'.) Dietary guidance — The optimal dietary intake during diarrheal illnesses has not been established. Controversy exists about issues such as partial fasting, the composition of the diet, and the time at which solid food intake should be resumed. Ultimately, apart from hydration, diet is not likely to be important, since disease duration is only a few days. The most important intervention for someone with travelers' diarrhea is to maintain hydration. In general, we advise individuals to eat or not as they choose, depending on how hungry they are. Often someone with diarrhea will not feel hungry, but if they do choose to eat, will prefer a bland diet such as rice or toast. A restricted diet (eg, beginning with only clear liquids to match diarrheal losses during the acute phase of diarrhea) is often recommended. A randomized trial among healthy American students being treated with antibiotics for travelers' diarrhea in Mexico compared the effects of this restricted diet with an unrestricted diet (in which the only specific recommendation was to match fluid intake to diarrheal losses) [20]. The mean duration of diarrhea (37 versus 33 hours) and the course of clinical symptoms were similar in the two groups. The general applicability of these observations is uncertain. Antibiotics Indications — We suggest not treating most cases of travelers' diarrhea with antibiotics. Antibiotic treatment is reasonable for travelers with severe diarrhea, which is characterized by fever and blood, pus, or mucus in the stool, or for travelers with diarrhea that substantially interferes with the purpose of travel. Antibiotic treatment can reduce the duration of travelers' diarrhea from several days to one or two days. However, drawbacks to antibiotics include cost, potential side effects, and promotion of bacterial resistance, which is an increasing concern. The benefit of antibiotics may not outweigh the drawbacks in many individuals with travelers' diarrhea. Caution should be used when treating a patient who has grossly bloody diarrhea with antibiotics, particularly if there is no or minimal fever. Although an uncommon cause of travelers' diarrhea, bloody diarrhea can reflect infection with enterohemorrhagic E. coli, for which antibiotic treatment has been associated with an increased risk of hemolytic-uremic syndrome, especially in children. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment", section on 'Antibiotics'.) Selection — Several different antibiotic options are effective for travelers' diarrhea (table 1). In general, we use azithromycin or a fluoroquinolone. In particular, azithromycin is the preferred option for patients with fever or dysentery (bloody or mucoid diarrhea), pregnant women, children, and for travelers to locations (such as Southeast Asia) where fluoroquinolone-resistant pathogens are prevalent. Fluoroquinolones had long been the first choice for treatment of travelers' diarrhea, https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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but the emergence of resistance to this drug class and increased awareness of adverse events make the risk-benefit assessment less clear. Rifaximin and rifamycin are alternatives for travelers' diarrhea suspected to be caused by noninvasive strains of E. coli, but their effectiveness against invasive pathogens is unknown, and they should not be used in patients with fever or bloody diarrhea. Widespread antibiotic resistance among many routine enteric pathogens to drugs such as ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX) has made these agents less useful for the treatment of travelers' diarrhea in much of the world [21-23]. In addition, organisms such as Campylobacter spp or any of the vibrios would not be expected to be sensitive to these agents. Azithromycin — Azithromycin is an effective drug for the treatment of travelers' diarrhea and is the preferred agent for patients with fever or dysentery (bloody or mucoid diarrhea), pregnant women, children (10 mg/kg/day up to a maximum dose of 500 mg for 3 days), and travelers (table 1) to locations, such as Southeast Asia, where quinolone-resistant C. jejuni is a common cause. However, the most effective and practical dose (a single 1 g dose) causes nausea in some individuals. A three-day course of 500 mg daily is also effective. Evidence of efficacy has been provided by studies from Mexico [24], Turkey [25], Thailand [21,26], and other regions [27]. In randomized controlled trials of American adults with travelers' diarrhea in Mexico and Turkey, a single 1000 mg oral dose of azithromycin was as effective as a single 500 mg dose of levofloxacin [24,25]. In the trial from Turkey, azithromycin was associated with a greater likelihood of nausea than levofloxacin in the first 30 minutes after dosing (8 versus 1 percent) [25]. Azithromycin may be superior to the fluoroquinolones for travelers' diarrhea in areas where fluoroquinolone resistance has been increasing. A randomized trial performed in Thailand compared azithromycin, given as a single 1 g dose or 500 mg/day for three days, with levofloxacin (500 mg/day for 3 days) in 156 United States military personnel [26]. C. jejuni was responsible for 64 percent of cases and was quinolone-resistant in 50 percent. Azithromycin administered as a single 1 g dose had a higher cure rate than a three day regimen of either azithromycin (500 mg daily) or levofloxacin (500 mg daily); cure rates were 96, 85, and 71 percent, respectively. Microbiologic eradication was much higher with azithromycin (96 to 100 percent versus 38 percent with levofloxacin), but this difference correlated poorly with outcome. Fluoroquinolones — Fluoroquinolones have well established efficacy for travelers' diarrhea (table 1). They are active against the majority of enterotoxigenic E. coli strains and also have activity against less common but potential pathogens, such as Campylobacter spp, Salmonella spp, and Vibrio parahaemolyticus [28,29]. However, there is increasingly frequent resistance to quinolones among diarrheal pathogens worldwide, particularly C. jejuni isolates in Southeast Asia [30-34]. Furthermore, greater awareness of adverse effects associated with fluoroquinolones https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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dampens enthusiasm for their use. Specifically, in the United States, the Food and Drug Administration released a statement about disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system related to fluoroquinolone use [35] and advised that they not be prescribed unless the benefits outweigh the risks. Fluoroquinolones should also not be used for travelers' diarrhea in pregnant women or children. Fluoroquinolones will lead to resolution of diarrheal symptoms in the majority of travelers within one day [36-40]. In two randomized trials, for example, ciprofloxacin (500 mg twice daily) resulted in a mean duration of diarrhea of 1.5 days compared with 2.9 days with placebo [39], and norfloxacin (400 mg twice daily for three days) resulted in a mean duration of diarrhea of 1.2 days compared with 3.3 days with placebo [37]. Although two to three days of treatment should be sufficient for the majority of episodes of travelers' diarrhea, a single dose of ciprofloxacin or norfloxacin may also be effective [40]. Rifaximin and rifamycin — Rifaximin (200 mg three times daily for three days for children ≥12 years of age and adults) and rifamycin (two 194 mg tablets twice daily for three days for adults) are poorly absorbed drugs from the rifamycin class that are alternatives for travelers' diarrhea caused by noninvasive strains of E. coli. We reserve their use for patients in whom fluoroquinolones or azithromycin are not available or appropriate since Campylobacter spp are generally resistant to rifamycins and their efficacy in the setting of invasive diarrhea (bloody diarrhea and/or fever) has not been established. ●
In controlled trials, rifaximin was associated with more rapid cessation of diarrhea than placebo [41] and had equal efficacy to fluoroquinolones [27,42,43]. Rifaximin combined with loperamide may provide more rapid symptomatic improvement than either agent alone [44].
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In preliminary results from a randomized trial, rifamycin resulted in a higher cure rate than placebo (81 versus 54 percent), with headache and constipation as the most common adverse effects [45].
Symptomatic therapy — Non-antibiotic symptomatic management (eg, bismuth or antimotility agents such as loperamide or diphenoxylate) can be used for mild or moderate diarrhea. For travelers with severe diarrhea, we suggest that antimotility agents only be taken in conjunction with antibiotics. Probiotics are often used for patients with infectious diarrhea. Studies overall suggest a modest reduction in the duration of diarrhea with certain probiotics, but results of studies done with a particular agent cannot be generalized to indicate that any probiotic agent would be successful in the same clinical situation. This is discussed in detail elsewhere. (See "Probiotics for gastrointestinal diseases", section on 'Infectious diarrhea'.) Antimotility agents — Antimotility agents, such as loperamide (Imodium) or diphenoxylate (Lomotil), can be used by travelers to reduce the rate of stooling; they do not treat the cause of https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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diarrhea. Antimotility agents can be used alone (ie, without antibiotics) in mild to moderate travelers' diarrhea. For travelers with severe diarrhea, we suggest that antimotility agents (such as loperamide or diphenoxylate) only be taken in conjunction with antibiotics. Furthermore, travelers should be educated about the need to avoid antimotility agents in dysentery (bloody stool and/or fevers). Antimotility agents should be stopped if abdominal pain or other symptoms worsen or if the diarrhea continues to be intractable after two days. Particular vigilance about hydration is important in patients who take antimotility agents for travelers' diarrhea, as the agents do not kill the pathogen causing the diarrhea or stop the secretory process in the intestine. Patients may be unaware of how much fluid they are losing into their intestine since they are no longer having frequent bowel movements. Additionally, there continues to be some concern that antimotility agents can prolong some types of dysenteric illnesses (eg, Shigella) [46]. While some studies suggest that antimotility drugs can be safely used in dysenteric illnesses as long as they are combined with antibiotic therapy, none of the studies evaluating the benefit of antimotility agents included in a 2008 meta-analysis included patients with bloody diarrhea or symptoms suggestive of dysentery [38,47,48]. The antisecretory drug, racecadotril, which is not available in the United States, may be useful in travelers' diarrhea. Bismuth — Bismuth subsalicylate can also be used to treat the symptoms of diarrhea, although large doses are required. Sixty mL (or four tablets) should be taken every one-half hour until the diarrhea resolves or eight doses have been taken. The two major disadvantages of this type of treatment are the potential for salicylate toxicity (especially in those who take aspirin for any reason, pregnant women, and children) and the need to carry large quantities of bismuth subsalicylate.
PATIENTS WITH PERSISTENT DIARRHEA For patients with diarrhea that has persisted for more than 10 to 14 days or for those whose diarrhea does not improve with antibiotic therapy, less common or drug-resistant pathogens may be causative. In a study of 7442 returning travelers who sought care at a GeoSentinel Network site and were diagnosed with an infectious gastrointestinal disease (not limited to diarrhea), 2092 cases had a pathogen identified on testing [49]. In 65 percent of those cases, a parasite was isolated. The most commonly isolated pathogens were Giardia spp (28 percent), Campylobacter spp (13 percent), Entamoeba histolytica (13 percent), Shigella spp (6 percent), and Strongyloides (6 percent). Cyclospora, Isospora, Cryptosporidium, and microsporidia are also thought to be important causes, but may be underestimated because of difficulty in identifying them [50]. In travelers who had taken antibiotics, C. difficile is another possibility.
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For such patients, evaluation focuses on identifying the infecting pathogen so that therapy can be targeted. In addition to a stool culture, this includes examination of stool for ova and parasites. Specialized staining techniques, such as a modified acid fast or trichome stain, may be required for certain organisms, such as Cryptosporidium parvum, microsporidia, Cyclospora, and Isospora. Stool antigen testing is also available for some parasites, such as Giardia and Entamoeba spp. Multiplex polymerase chain reaction assays for identification of a variety of enteropathogens are also available, but interpretation may be confounded by the identification of more than one pathogenic organism. Diagnosis and treatment of these organisms are discussed in the dedicated topic reviews. In some cases, persistent diarrhea may be representative of a previously undiagnosed noninfectious cause or a post-infectious irritable bowel syndrome. The approach to this is discussed in detail elsewhere. (See "Approach to the adult with chronic diarrhea in resource-rich settings" and "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)
SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults" and "Society guideline links: Acute diarrhea in children" and "Society guideline links: Travel medicine".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-toread materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) ●
Beyond the Basics topics (see "Patient education: General travel advice (Beyond the Basics)" and "Patient education: Foodborne illness (food poisoning) (Beyond the Basics)" and "Patient education: Giardia (Beyond the Basics)" and "Patient education: Travelers' diarrhea (The Basics)")
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SUMMARY AND RECOMMENDATIONS ●
The classic travelers' diarrhea due to enterotoxigenic Escherichia coli (ETEC) generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. The illness is generally self-limited with symptoms lasting for approximately one to five days. (See 'Classic symptoms' above and 'Timing' above.)
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Less common symptoms of colitis (tenesmus, urgency, cramping, and bloody diarrhea), belching, or profuse watery diarrhea may reflect other infectious etiologies of travelers' diarrhea. (See 'Symptoms associated with specific etiologies' above.)
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The diagnosis of travelers' diarrhea is made in an individual from a resource-rich setting who develops unformed stools during or shortly after returning from travel to a resource-limited setting. Travelers' diarrhea is typically self-diagnosed by the patient. Determination of the infectious agent is generally unnecessary. Microbiologic workup is generally reserved for patients with systemic illness, fever and colitis, prominent upper intestinal symptoms (in whom giardiasis is more likely), and a recent history of antibiotic use. (See 'Diagnosis and evaluation' above.)
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Travelers from resource-rich settings who develop diarrhea while traveling to resource-limited settings generally should treat themselves rather than seek medical advice while traveling. The primary and most important treatment of travelers' (or any other) diarrhea is fluid replacement, since the most significant risk of diarrhea is volume depletion. Fluid replacement can be done with general fluids or with oral rehydration solutions, depending on the severity of the illness. (See 'Fluid replacement' above.)
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Antibiotic treatment can reduce the duration of travelers' diarrhea from several days to one or two days. However, the benefits of antibiotics should be weighed against the potential risks, including adverse effects and promotion of bacterial resistance. For most individuals with travelers' diarrhea, we suggest not treating with antibiotics (Grade 2B). Antibiotic therapy is appropriate for travelers with severe diarrhea characterized by fever and blood, pus, or mucus in the stool, or diarrhea of any severity that substantially interferes with the purpose of travel. (See 'Indications' above.)
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For patients who warrant empiric antibiotic therapy for travelers' diarrhea, we suggest azithromycin or a fluoroquinolone (Grade 2B). Azithromycin is preferred for patients with fever or dysentery (bloody or mucoid diarrhea), children, pregnant women, and travelers to Asia. Rifaximin and rifamycin are alternative agents, but should be avoided in patients with features of invasive diarrhea (eg, bloody or mucoid stool) (See 'Selection' above.)
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Non-antibiotic symptomatic management (eg, bismuth or antimotility agents such as loperamide or diphenoxylate) can be used for mild or moderate diarrhea. For travelers with
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severe diarrhea, we suggest that antimotility agents only be taken in conjunction with antibiotics (Grade 2C). Because they address the symptoms but not the cause, antimotility agents can mask the amount of fluid lost into the intestine. Additionally, there is concern that they can prolong or exacerbate dysentery. These agents should be discontinued promptly if abdominal pain develops, other symptoms worsen, or diarrhea persists. (See 'Symptomatic therapy' above.) ●
For patients with diarrhea that has persisted for more than 10 to 14 days or for those whose diarrhea does not improve with antibiotic therapy, less common or drug-resistant pathogens may be causative. For such patients, evaluation focuses on identifying the infecting pathogen so that therapy can be targeted. In addition to a stool culture, this includes examination of stool for ova and parasites. (See 'Patients with persistent diarrhea' above.)
ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Christine A Wanke, MD, who contributed to an earlier version of this topic review.
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7. Lübbert C, Straube L, Stein C, et al. Colonization with extended-spectrum beta-lactamaseproducing and carbapenemase-producing Enterobacteriaceae in international travelers returning to Germany. Int J Med Microbiol 2015; 305:148. 8. Kantele A, Lääveri T, Mero S, et al. Antimicrobials increase travelers' risk of colonization by extended-spectrum betalactamase-producing Enterobacteriaceae. Clin Infect Dis 2015; 60:837. 9. Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med 2017; 24:S57. 10. von Sonnenburg F, Tornieporth N, Waiyaki P, et al. Risk and aetiology of diarrhoea at various tourist destinations. Lancet 2000; 356:133. 11. Soonawala D, Vlot JA, Visser LG. Inconvenience due to travelers' diarrhea: a prospective follow-up study. BMC Infect Dis 2011; 11:322. 12. Steffen R, Collard F, Tornieporth N, et al. Epidemiology, etiology, and impact of traveler's diarrhea in Jamaica. JAMA 1999; 281:811. 13. Rendi-Wagner P, Kollaritsch H. Drug prophylaxis for travelers' diarrhea. Clin Infect Dis 2002; 34:628. 14. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis 2017; 65:e45. 15. Antikainen J, Kantele A, Pakkanen SH, et al. A quantitative polymerase chain reaction assay for rapid detection of 9 pathogens directly from stools of travelers with diarrhea. Clin Gastroenterol Hepatol 2013; 11:1300. 16. Avery ME, Snyder JD. Oral therapy for acute diarrhea. The underused simple solution. N Engl J Med 1990; 323:891. 17. Carpenter CC, Greenough WB, Pierce NF. Oral-rehydration therapy--the role of polymeric substrates. N Engl J Med 1988; 319:1346. 18. Caeiro JP, DuPont HL, Albrecht H, Ericsson CD. Oral rehydration therapy plus loperamide versus loperamide alone in the treatment of traveler's diarrhea. Clin Infect Dis 1999; 28:1286. 19. de Zoysa I, Kirkwood B, Feachem R, Lindsay-Smith E. Preparation of sugar-salt solutions. Trans R Soc Trop Med Hyg 1984; 78:260.
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20. Huang DB, Awasthi M, Le BM, et al. The role of diet in the treatment of travelers' diarrhea: a pilot study. Clin Infect Dis 2004; 39:468. 21. Kuschner RA, Trofa AF, Thomas RJ, et al. Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent. Clin Infect Dis 1995; 21:536. 22. Murray BE. Resistance of Shigella, Salmonella, and other selected enteric pathogens to antimicrobial agents. Rev Infect Dis 1986; 8 Suppl 2:S172. 23. Murray BE, Mathewson JJ, DuPont HL, et al. Emergence of resistant fecal Escherichia coli in travelers not taking prophylactic antimicrobial agents. Antimicrob Agents Chemother 1990; 34:515. 24. Adachi JA, Ericsson CD, Jiang ZD, et al. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis 2003; 37:1165. 25. Sanders JW, Frenck RW, Putnam SD, et al. Azithromycin and loperamide are comparable to levofloxacin and loperamide for the treatment of traveler's diarrhea in United States military personnel in Turkey. Clin Infect Dis 2007; 45:294. 26. Tribble DR, Sanders JW, Pang LW, et al. Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3day levofloxacin regimen. Clin Infect Dis 2007; 44:338. 27. Riddle MS, Connor P, Fraser J, et al. Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide. Clin Infect Dis 2017; 65:2008. 28. Steffen R. Epidemiologic studies of travelers' diarrhea, severe gastrointestinal infections, and cholera. Rev Infect Dis 1986; 8 Suppl 2:S122. 29. From the Centers for Disease Control. Cholera--international travel, 1992. JAMA 1992; 268:1648. 30. Smith KE, Besser JM, Hedberg CW, et al. Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998. Investigation Team. N Engl J Med 1999; 340:1525. 31. Hakanen A, Jousimies-Somer H, Siitonen A, et al. Fluoroquinolone resistance in Campylobacter jejuni isolates in travelers returning to Finland: association of ciprofloxacin resistance to travel destination. Emerg Infect Dis 2003; 9:267.
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32. Nachamkin I, Ung H, Li M. Increasing fluoroquinolone resistance in Campylobacter jejuni, Pennsylvania, USA,1982-2001. Emerg Infect Dis 2002; 8:1501. 33. Sanders JW, Isenbarger DW, Walz SE, et al. An observational clinic-based study of diarrheal illness in deployed United States military personnel in Thailand: presentation and outcome of Campylobacter infection. Am J Trop Med Hyg 2002; 67:533. 34. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med 2006; 355:2452. 35. US Food and Drug Administration. FDA Drug Safety Communication: FDA updates and war nings for oral and injectable fluoroquinolone antibiotics due to disabling side effects, 2016. ht tps://www.fda.gov/downloads/Drugs/DrugSafety/UCM513019.pdf (Accessed on November 1 5, 2017). 36. DuPont HL, Ericsson CD. Prevention and treatment of traveler's diarrhea. N Engl J Med 1993; 328:1821. 37. Mattila L, Peltola H, Siitonen A, et al. Short-term treatment of traveler's diarrhea with norfloxacin: a double-blind, placebo-controlled study during two seasons. Clin Infect Dis 1993; 17:779. 38. Taylor DN, Sanchez JL, Candler W, et al. Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial. Ann Intern Med 1991; 114:731. 39. Pichler HE, Diridl G, Stickler K, Wolf D. Clinical efficacy of ciprofloxacin compared with placebo in bacterial diarrhea. Am J Med 1987; 82:329. 40. Salam I, Katelaris P, Leigh-Smith S, Farthing MJ. Randomised trial of single-dose ciprofloxacin for travellers' diarrhoea. Lancet 1994; 344:1537. 41. Steffen R, Sack DA, Riopel L, et al. Therapy of travelers' diarrhea with rifaximin on various continents. Am J Gastroenterol 2003; 98:1073. 42. DuPont HL, Jiang ZD, Ericsson CD, et al. Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial. Clin Infect Dis 2001; 33:1807. 43. Adachi JA, DuPont HL. Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. Clin Infect Dis 2006; 42:541. 44. Dupont HL, Jiang ZD, Belkind-Gerson J, et al. Treatment of travelers' diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone. Clin Gastroenterol Hepatol 2007; 5:451.
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45. Study to Evaluate Safety and Efficacy of Rifamycin SV Multi-Matrix System (MMX) for the Tr eatment of Traveler's Diarrhea (TD). ClinicalTrials.gov Identifier: NCT01142089 https://clinica ltrials.gov/ct2/show/results/NCT01142089?view=results. 46. DuPont HL, Hornick RB. Adverse effect of lomotil therapy in shigellosis. JAMA 1973; 226:1525. 47. Petruccelli BP, Murphy GS, Sanchez JL, et al. Treatment of traveler's diarrhea with ciprofloxacin and loperamide. J Infect Dis 1992; 165:557. 48. Riddle MS, Arnold S, Tribble DR. Effect of adjunctive loperamide in combination with antibiotics on treatment outcomes in traveler's diarrhea: a systematic review and metaanalysis. Clin Infect Dis 2008; 47:1007. 49. Swaminathan A, Torresi J, Schlagenhauf P, et al. A global study of pathogens and host risk factors associated with infectious gastrointestinal disease in returned international travellers. J Infect 2009; 59:19. 50. Ross AG, Olds GR, Cripps AW, et al. Enteropathogens and chronic illness in returning travelers. N Engl J Med 2013; 368:1817.
Topic 99648 Version 16.0
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GRAPHICS Oral agents for self-treatment of travelers' diarrhea in adults Agent Azithromycin
Dose 1000 mg once
500 mg once daily
Duration Single dose*
Comment
Preferred for dysentery or febrile diarrhea, travelers from Southeast Asia, and pregnant women
Three-day course
The 1000 mg dose may be associated with nausea Levofloxacin
500 mg once daily
Single dose* or three-day course
Ciprofloxacin
750 mg once
Single dose*
500 mg twice daily
Three-day course
Ofloxacin
400 mg once daily
Single dose* or three-day course
Rifaximin
200 mg three times daily
Three-day course
Rifamycin
Two (194 mg) tablets twice daily
Three-day course
Fluoroquinolones are associated with multiple adverse events
Not for use with dysentery or febrile diarrhea
* If symptoms have not resolved after 24 hours, the regimen can be extended to complete a three-day course (using the dosing listed for the three-day course). Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med 2017; 24:S57. Graphic 75355 Version 8.0
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Contributor Disclosures Regina LaRocque, MD, MPH Nothing to disclose Jason B Harris, MD, MPH Consultant/Advisory Boards: Scientific Advisory Committee [Cholera (Oral cholera vaccine)]. Stephen B Calderwood, MD Consultant/Advisory Boards: Day Zero Diagnostics [Whole genome sequencing for microbial identification and determination of antimicrobial susceptibility]. Equity Ownership: Pulmatrix [Infectious diseases (Inhaled antimicrobials)]. Allyson Bloom, MD Nothing to disclose Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy
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Official reprint from UpToDate® www.uptodate.com ©2019 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment Authors: Regina LaRocque, MD, MPH, Jason B Harris, MD, MPH Section Editor: Stephen B Calderwood, MD Deputy Editor: Allyson Bloom, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Aug 2019. | This topic last updated: Dec 03, 2018.
INTRODUCTION Travelers' diarrhea is the most common illness in persons traveling from resource-rich to resourcelimited regions of the world [1,2]. Among travelers to such areas, 40 to 60 percent develop diarrhea [3]. Episodes of travelers' diarrhea are nearly always benign and self-limited, but symptoms may disrupt planned activities and result in health care visits for some travelers [4]. There is a growing recognition that travelers' diarrhea and its self-treatment abroad are associated with the acquisition of organisms harboring antibiotic resistance [5-8]. The clinical features, diagnosis and evaluation, and treatment of travelers' diarrhea are discussed here. The microbiology, epidemiology, and prevention of travelers' diarrhea are discussed elsewhere. (See "Travelers' diarrhea: Microbiology, epidemiology, and prevention".)
DEFINITIONS Travelers' diarrhea refers to diarrhea that develops in individuals from resource-rich settings during or within 10 days of returning from travel to resource-limited countries or regions. Clinically, the severity of travelers' diarrhea can be categorized according to a classification scheme suggested by an expert panel of the International Society of Travel Medicine, which uses functional impact to define severity [9]: ●
Mild – Diarrhea that is tolerable, is not distressing, and does not interfere with planned activities
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Moderate – Diarrhea that is distressing or interferes with planned activities
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Severe – Diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools) is considered severe
For epidemiologic purposes, travelers' diarrhea has frequently been categorized into three forms: classic, moderate, and mild. These forms of travelers' diarrhea are defined as follows [10]: ●
Classic – Passage of three or more unformed stools in a 24 hour period plus at least one of these other symptoms: nausea, vomiting, abdominal pain or cramps, fever, blood in stools
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Moderate – Passage of one or two unformed stools in 24 hours plus at least one of the above symptoms or more than two unformed stools in 24 hours without other symptoms
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Mild – Passage of one or two unformed stools in 24 hours without other symptoms
These definitions allow some uniformity in studies of the epidemiology and etiologies of travelers' diarrhea. For such studies, the three types can be grouped together to estimate a total number of cases of travelers' diarrhea. (See "Evaluation of fever in the returning traveler".)
CLINICAL MANIFESTATIONS Classic symptoms — The symptoms of travelers' diarrhea depend upon the microbial etiology. The classic "turista" due to enterotoxigenic Escherichia coli (ETEC) generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. Very frequent stools are uncommon. Nausea and vomiting also may occur. Typically there are no symptoms of colitis such as blood or pus in the stool. Patients may develop a low grade fever. As an example, in a prospective study of 390 travelers from the Netherlands to subtropical and tropical regions, 160 (41 percent) reported travelers' diarrhea (defined as three or more unformed stools within a 24 hour period) on post-travel questionnaires [11]. Of those with diarrhea, 86 percent reported watery stools, 77 percent abdominal discomfort or cramps, and 71 percent fecal urgency. Twenty percent reported vomiting, and only 11 percent had a fever. Most had three to five stools per day; three percent had >10 stools per day. Ten percent reported only loose stools without accompanying symptoms. While it is common to be unable to proceed with planned activities, only a minority of patients report requiring bedrest for one to two days. In a series of 30,369 travelers to Jamaica, among whom the attack rate for travelers' diarrhea was 24 percent, incapacity was reported for a mean of 11.6 hours from the illness onset [12]. Symptoms associated with specific etiologies — Even when other bacterial agents such as Campylobacter jejuni and Shigella spp are implicated, the symptoms initially experienced by the traveler are generally similar to those seen with ETEC. However, infections with these organisms may progress to include symptoms of colitis, such as fever, tenesmus, urgency, cramping, and https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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bloody diarrhea. (See "Clinical manifestations, diagnosis, and treatment of Campylobacter infection" and "Shigella infection: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.) Belching and other upper intestinal symptoms are typical of giardiasis, while profuse watery diarrhea is characteristic of cholera, cryptosporidiosis, and Cyclospora cayetanensis infection. The symptoms of microsporidiosis may be more subtle with bloating and intermittent diarrhea. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis" and "Epidemiology, clinical manifestations, and diagnosis of cryptosporidiosis" and "Microsporidiosis" and "Cyclospora infection".) Timing — Most episodes of travelers' diarrhea occur between 4 and 14 days after arrival [12], but travelers' diarrhea can occur within a much shorter time frame if the concentration of bacteria ingested is sufficiently high. The illness is generally self-limited with symptoms lasting for approximately one to five days. However, 8 to 15 percent of patients experience symptoms for more than one week and as many as two percent for more than one month [13]. Long-term sequelae — Subsequent development of chronic gastrointestinal symptoms, and in particular irritable bowel syndrome, has been reported in a sizable minority of patients following travelers' diarrhea. Postinfectious irritable bowel syndrome is discussed in detail elsewhere. (See "Pathophysiology of irritable bowel syndrome", section on 'Postinfectious'.)
DIAGNOSIS AND EVALUATION The diagnosis of travelers' diarrhea is made in an individual who develops unformed stools during or shortly after returning from travel to a resource-limited setting. Travelers' diarrhea is typically self-diagnosed. For those who present to medical care after returning home with uncomplicated travelers' diarrhea, determination of the microbiologic agent is generally unnecessary [14]. Management of travelers' diarrhea is often symptomatic and initiated without regard to the specific offending agent. Furthermore, routine stool cultures are rarely informative since ETEC and enteroaggregative E. coli (EAEC) cannot be distinguished from nonpathogenic E. coli on stool culture, and viral agents would not be identified with stool cultures. Culture-independent diagnostic testing, such as antigen-based molecular assays, is available but not yet in routine clinical use; its application may be limited by the identification of multiple potential pathogens [15] and the lack of associated antibiotic sensitivity testing. However, certain features may warrant a specific microbiologic workup that could potentially lead to targeted treatment. (See "Approach to the adult with acute diarrhea in resource-rich settings" and "Approach to diarrhea in children in resource-rich countries".) https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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In patients with fever and symptoms of colitis (bloody or mucoid stools, abdominal cramping), a stool culture should be performed to evaluate for Campylobacter or Shigella spp. If available, stool can also be tested for enterohemorrhagic E. coli and Shiga toxin. (See "Clinical manifestations, diagnosis, and treatment of Campylobacter infection", section on 'Diagnosis' and "Shigella infection: Clinical manifestations and diagnosis", section on 'Diagnosis' and "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)
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In patients with predominantly upper gastrointestinal symptoms (eg, bloating, gas, nausea), stool examination for Giardia lamblia, Cyclospora, and Isospora should be undertaken. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Cyclospora infection", section on 'Diagnosis'.)
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Travelers who have taken antibiotics in the preceding 8 to 12 weeks are at risk for Clostridioides (formerly Clostridium) difficile diarrhea and should be tested for this pathogen. (See "Clostridioides (formerly Clostridium) difficile infection in adults: Clinical manifestations and diagnosis", section on 'Diagnosis'.)
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In patients who appear systemically ill, blood cultures should be taken to evaluate for Salmonella species, including Salmonella typhi. (See "Nontyphoidal Salmonella bacteremia" and "Epidemiology, microbiology, clinical manifestations, and diagnosis of enteric (typhoid and paratyphoid) fever", section on 'Diagnosis'.)
Additional workup may be warranted in individuals who have persistent diarrhea beyond 10 to 14 days, including consideration of testing for intestinal parasitic infections [14]. (See 'Patients with persistent diarrhea' below.)
DIFFERENTIAL DIAGNOSIS Acute diarrhea in travelers from resource-limited settings is most frequently caused by gastrointestinal infection. Diarrhea may also occur in the context of systemic infections, such as influenza, HIV infection, dengue fever, and malaria. Other non-infectious food-poisoning syndromes, such as shellfish or mushroom poisoning can cause diarrhea. These other syndromes can be differentiated from simple travelers' diarrhea by the presence of other distinguishing clinical features or specific diagnostic testing. (See "Evaluation of fever in the returning traveler" and "Overview of shellfish and pufferfish poisoning", section on 'Diarrheic shellfish poisoning' and "Clinical manifestations and evaluation of mushroom poisoning", section on 'Acute gastroenteritis'.) Additionally, new medications may be a cause of acute diarrhea in travelers; comparing the timing of initiation with the onset of diarrhea can help evaluate for this noninfectious etiology of diarrhea. https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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MANAGEMENT Management of travelers' diarrhea depends on the severity of illness. Fluid replacement is an essential component of treatment for all cases of travelers' diarrhea. Most cases are self-limited and resolve on their own within three to five days of treatment with fluid replacement only. Antibiotics and antimotility agents, often used together, may be warranted in certain circumstances. Antimicrobial therapy shortens the disease duration to about one day and antimotility agents may limit symptoms to a period of hours. Antimicrobial choice depends, in part, on the region of travel. The benefit of antibiotics must be weighed against potential risks, including adverse effects and selection for resistant bacteria. These issues are discussed in the sections that follow. When to seek care — Travelers from resource rich settings who develop diarrhea while traveling to resource limited settings generally can treat themselves rather than seek medical advice while traveling. However, medical evaluation may be warranted in patients who develop high fever, abdominal pain, bloody diarrhea, or vomiting and for whom empiric antibiotics have not been of benefit. Otherwise, for most patients while traveling or after returning home, medical consultation is generally not warranted unless symptoms persist for 10 to 14 days. Fluid replacement — The primary and most important treatment of travelers' (or any other) diarrhea is fluid replacement, since the most significant complication of diarrhea is volume depletion [16,17]. The approach to fluid replacement depends on the severity of the diarrhea and volume depletion. Travelers can use the amount of urine passed as a general guide to their level of volume depletion. If they are urinating regularly, even if the color is dark yellow, the diarrhea and volume depletion are likely mild. If there is a paucity of urine and that small amount is dark yellow, the diarrhea and volume depletion are likely more severe. ●
Mild cases – Patients with mild diarrhea may combine alternating sips of fluids that contain salt and fluids that contain sugar to replete and maintain hydration. Broth, fruit juice, or similar fluids may be used. Pedialyte is frequently useful in children. For mild diarrhea, the use of fluids is the critical factor; the fluid need not be oral rehydration solution. One study showed no difference in outcome between treatment with oral rehydration solution plus loperamide versus generic fluids and loperamide [18].
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Severe cases – Severe diarrhea should be treated with oral rehydration solution (ORS); this replaces needed electrolytes in the appropriate concentrations. Packets of oral rehydration solution are available in the pharmacies of most countries and can be mixed with clean drinking water [19]. ORS should be used until the individual is urinating regularly. Alternatively, a similar solution can be made by adding 1/2 teaspoon of salt, 1/2 teaspoon of baking soda, and 4 tablespoons of sugar to one liter of water. The electrolyte concentrations of fluids used for sweat replacement (eg, Gatorade) are not equivalent. (See "Approach to the
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adult with acute diarrhea in resource-rich settings", section on 'Fluid repletion' and "Oral rehydration therapy", section on 'Clinical management'.) Dietary guidance — The optimal dietary intake during diarrheal illnesses has not been established. Controversy exists about issues such as partial fasting, the composition of the diet, and the time at which solid food intake should be resumed. Ultimately, apart from hydration, diet is not likely to be important, since disease duration is only a few days. The most important intervention for someone with travelers' diarrhea is to maintain hydration. In general, we advise individuals to eat or not as they choose, depending on how hungry they are. Often someone with diarrhea will not feel hungry, but if they do choose to eat, will prefer a bland diet such as rice or toast. A restricted diet (eg, beginning with only clear liquids to match diarrheal losses during the acute phase of diarrhea) is often recommended. A randomized trial among healthy American students being treated with antibiotics for travelers' diarrhea in Mexico compared the effects of this restricted diet with an unrestricted diet (in which the only specific recommendation was to match fluid intake to diarrheal losses) [20]. The mean duration of diarrhea (37 versus 33 hours) and the course of clinical symptoms were similar in the two groups. The general applicability of these observations is uncertain. Antibiotics Indications — We suggest not treating most cases of travelers' diarrhea with antibiotics. Antibiotic treatment is reasonable for travelers with severe diarrhea, which is characterized by fever and blood, pus, or mucus in the stool, or for travelers with diarrhea that substantially interferes with the purpose of travel. Antibiotic treatment can reduce the duration of travelers' diarrhea from several days to one or two days. However, drawbacks to antibiotics include cost, potential side effects, and promotion of bacterial resistance, which is an increasing concern. The benefit of antibiotics may not outweigh the drawbacks in many individuals with travelers' diarrhea. Caution should be used when treating a patient who has grossly bloody diarrhea with antibiotics, particularly if there is no or minimal fever. Although an uncommon cause of travelers' diarrhea, bloody diarrhea can reflect infection with enterohemorrhagic E. coli, for which antibiotic treatment has been associated with an increased risk of hemolytic-uremic syndrome, especially in children. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment", section on 'Antibiotics'.) Selection — Several different antibiotic options are effective for travelers' diarrhea (table 1). In general, we use azithromycin or a fluoroquinolone. In particular, azithromycin is the preferred option for patients with fever or dysentery (bloody or mucoid diarrhea), pregnant women, children, and for travelers to locations (such as Southeast Asia) where fluoroquinolone-resistant pathogens are prevalent. Fluoroquinolones had long been the first choice for treatment of travelers' diarrhea, https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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but the emergence of resistance to this drug class and increased awareness of adverse events make the risk-benefit assessment less clear. Rifaximin and rifamycin are alternatives for travelers' diarrhea suspected to be caused by noninvasive strains of E. coli, but their effectiveness against invasive pathogens is unknown, and they should not be used in patients with fever or bloody diarrhea. Widespread antibiotic resistance among many routine enteric pathogens to drugs such as ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX) has made these agents less useful for the treatment of travelers' diarrhea in much of the world [21-23]. In addition, organisms such as Campylobacter spp or any of the vibrios would not be expected to be sensitive to these agents. Azithromycin — Azithromycin is an effective drug for the treatment of travelers' diarrhea and is the preferred agent for patients with fever or dysentery (bloody or mucoid diarrhea), pregnant women, children (10 mg/kg/day up to a maximum dose of 500 mg for 3 days), and travelers (table 1) to locations, such as Southeast Asia, where quinolone-resistant C. jejuni is a common cause. However, the most effective and practical dose (a single 1 g dose) causes nausea in some individuals. A three-day course of 500 mg daily is also effective. Evidence of efficacy has been provided by studies from Mexico [24], Turkey [25], Thailand [21,26], and other regions [27]. In randomized controlled trials of American adults with travelers' diarrhea in Mexico and Turkey, a single 1000 mg oral dose of azithromycin was as effective as a single 500 mg dose of levofloxacin [24,25]. In the trial from Turkey, azithromycin was associated with a greater likelihood of nausea than levofloxacin in the first 30 minutes after dosing (8 versus 1 percent) [25]. Azithromycin may be superior to the fluoroquinolones for travelers' diarrhea in areas where fluoroquinolone resistance has been increasing. A randomized trial performed in Thailand compared azithromycin, given as a single 1 g dose or 500 mg/day for three days, with levofloxacin (500 mg/day for 3 days) in 156 United States military personnel [26]. C. jejuni was responsible for 64 percent of cases and was quinolone-resistant in 50 percent. Azithromycin administered as a single 1 g dose had a higher cure rate than a three day regimen of either azithromycin (500 mg daily) or levofloxacin (500 mg daily); cure rates were 96, 85, and 71 percent, respectively. Microbiologic eradication was much higher with azithromycin (96 to 100 percent versus 38 percent with levofloxacin), but this difference correlated poorly with outcome. Fluoroquinolones — Fluoroquinolones have well established efficacy for travelers' diarrhea (table 1). They are active against the majority of enterotoxigenic E. coli strains and also have activity against less common but potential pathogens, such as Campylobacter spp, Salmonella spp, and Vibrio parahaemolyticus [28,29]. However, there is increasingly frequent resistance to quinolones among diarrheal pathogens worldwide, particularly C. jejuni isolates in Southeast Asia [30-34]. Furthermore, greater awareness of adverse effects associated with fluoroquinolones https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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dampens enthusiasm for their use. Specifically, in the United States, the Food and Drug Administration released a statement about disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system related to fluoroquinolone use [35] and advised that they not be prescribed unless the benefits outweigh the risks. Fluoroquinolones should also not be used for travelers' diarrhea in pregnant women or children. Fluoroquinolones will lead to resolution of diarrheal symptoms in the majority of travelers within one day [36-40]. In two randomized trials, for example, ciprofloxacin (500 mg twice daily) resulted in a mean duration of diarrhea of 1.5 days compared with 2.9 days with placebo [39], and norfloxacin (400 mg twice daily for three days) resulted in a mean duration of diarrhea of 1.2 days compared with 3.3 days with placebo [37]. Although two to three days of treatment should be sufficient for the majority of episodes of travelers' diarrhea, a single dose of ciprofloxacin or norfloxacin may also be effective [40]. Rifaximin and rifamycin — Rifaximin (200 mg three times daily for three days for children ≥12 years of age and adults) and rifamycin (two 194 mg tablets twice daily for three days for adults) are poorly absorbed drugs from the rifamycin class that are alternatives for travelers' diarrhea caused by noninvasive strains of E. coli. We reserve their use for patients in whom fluoroquinolones or azithromycin are not available or appropriate since Campylobacter spp are generally resistant to rifamycins and their efficacy in the setting of invasive diarrhea (bloody diarrhea and/or fever) has not been established. ●
In controlled trials, rifaximin was associated with more rapid cessation of diarrhea than placebo [41] and had equal efficacy to fluoroquinolones [27,42,43]. Rifaximin combined with loperamide may provide more rapid symptomatic improvement than either agent alone [44].
●
In preliminary results from a randomized trial, rifamycin resulted in a higher cure rate than placebo (81 versus 54 percent), with headache and constipation as the most common adverse effects [45].
Symptomatic therapy — Non-antibiotic symptomatic management (eg, bismuth or antimotility agents such as loperamide or diphenoxylate) can be used for mild or moderate diarrhea. For travelers with severe diarrhea, we suggest that antimotility agents only be taken in conjunction with antibiotics. Probiotics are often used for patients with infectious diarrhea. Studies overall suggest a modest reduction in the duration of diarrhea with certain probiotics, but results of studies done with a particular agent cannot be generalized to indicate that any probiotic agent would be successful in the same clinical situation. This is discussed in detail elsewhere. (See "Probiotics for gastrointestinal diseases", section on 'Infectious diarrhea'.) Antimotility agents — Antimotility agents, such as loperamide (Imodium) or diphenoxylate (Lomotil), can be used by travelers to reduce the rate of stooling; they do not treat the cause of https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises recur…
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diarrhea. Antimotility agents can be used alone (ie, without antibiotics) in mild to moderate travelers' diarrhea. For travelers with severe diarrhea, we suggest that antimotility agents (such as loperamide or diphenoxylate) only be taken in conjunction with antibiotics. Furthermore, travelers should be educated about the need to avoid antimotility agents in dysentery (bloody stool and/or fevers). Antimotility agents should be stopped if abdominal pain or other symptoms worsen or if the diarrhea continues to be intractable after two days. Particular vigilance about hydration is important in patients who take antimotility agents for travelers' diarrhea, as the agents do not kill the pathogen causing the diarrhea or stop the secretory process in the intestine. Patients may be unaware of how much fluid they are losing into their intestine since they are no longer having frequent bowel movements. Additionally, there continues to be some concern that antimotility agents can prolong some types of dysenteric illnesses (eg, Shigella) [46]. While some studies suggest that antimotility drugs can be safely used in dysenteric illnesses as long as they are combined with antibiotic therapy, none of the studies evaluating the benefit of antimotility agents included in a 2008 meta-analysis included patients with bloody diarrhea or symptoms suggestive of dysentery [38,47,48]. The antisecretory drug, racecadotril, which is not available in the United States, may be useful in travelers' diarrhea. Bismuth — Bismuth subsalicylate can also be used to treat the symptoms of diarrhea, although large doses are required. Sixty mL (or four tablets) should be taken every one-half hour until the diarrhea resolves or eight doses have been taken. The two major disadvantages of this type of treatment are the potential for salicylate toxicity (especially in those who take aspirin for any reason, pregnant women, and children) and the need to carry large quantities of bismuth subsalicylate.
PATIENTS WITH PERSISTENT DIARRHEA For patients with diarrhea that has persisted for more than 10 to 14 days or for those whose diarrhea does not improve with antibiotic therapy, less common or drug-resistant pathogens may be causative. In a study of 7442 returning travelers who sought care at a GeoSentinel Network site and were diagnosed with an infectious gastrointestinal disease (not limited to diarrhea), 2092 cases had a pathogen identified on testing [49]. In 65 percent of those cases, a parasite was isolated. The most commonly isolated pathogens were Giardia spp (28 percent), Campylobacter spp (13 percent), Entamoeba histolytica (13 percent), Shigella spp (6 percent), and Strongyloides (6 percent). Cyclospora, Isospora, Cryptosporidium, and microsporidia are also thought to be important causes, but may be underestimated because of difficulty in identifying them [50]. In travelers who had taken antibiotics, C. difficile is another possibility.
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For such patients, evaluation focuses on identifying the infecting pathogen so that therapy can be targeted. In addition to a stool culture, this includes examination of stool for ova and parasites. Specialized staining techniques, such as a modified acid fast or trichome stain, may be required for certain organisms, such as Cryptosporidium parvum, microsporidia, Cyclospora, and Isospora. Stool antigen testing is also available for some parasites, such as Giardia and Entamoeba spp. Multiplex polymerase chain reaction assays for identification of a variety of enteropathogens are also available, but interpretation may be confounded by the identification of more than one pathogenic organism. Diagnosis and treatment of these organisms are discussed in the dedicated topic reviews. In some cases, persistent diarrhea may be representative of a previously undiagnosed noninfectious cause or a post-infectious irritable bowel syndrome. The approach to this is discussed in detail elsewhere. (See "Approach to the adult with chronic diarrhea in resource-rich settings" and "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)
SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults" and "Society guideline links: Acute diarrhea in children" and "Society guideline links: Travel medicine".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-toread materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) ●
Beyond the Basics topics (see "Patient education: General travel advice (Beyond the Basics)" and "Patient education: Foodborne illness (food poisoning) (Beyond the Basics)" and "Patient education: Giardia (Beyond the Basics)" and "Patient education: Travelers' diarrhea (The Basics)")
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Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment - UpToDate
SUMMARY AND RECOMMENDATIONS ●
The classic travelers' diarrhea due to enterotoxigenic Escherichia coli (ETEC) generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. The illness is generally self-limited with symptoms lasting for approximately one to five days. (See 'Classic symptoms' above and 'Timing' above.)
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Less common symptoms of colitis (tenesmus, urgency, cramping, and bloody diarrhea), belching, or profuse watery diarrhea may reflect other infectious etiologies of travelers' diarrhea. (See 'Symptoms associated with specific etiologies' above.)
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The diagnosis of travelers' diarrhea is made in an individual from a resource-rich setting who develops unformed stools during or shortly after returning from travel to a resource-limited setting. Travelers' diarrhea is typically self-diagnosed by the patient. Determination of the infectious agent is generally unnecessary. Microbiologic workup is generally reserved for patients with systemic illness, fever and colitis, prominent upper intestinal symptoms (in whom giardiasis is more likely), and a recent history of antibiotic use. (See 'Diagnosis and evaluation' above.)
●
Travelers from resource-rich settings who develop diarrhea while traveling to resource-limited settings generally should treat themselves rather than seek medical advice while traveling. The primary and most important treatment of travelers' (or any other) diarrhea is fluid replacement, since the most significant risk of diarrhea is volume depletion. Fluid replacement can be done with general fluids or with oral rehydration solutions, depending on the severity of the illness. (See 'Fluid replacement' above.)
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Antibiotic treatment can reduce the duration of travelers' diarrhea from several days to one or two days. However, the benefits of antibiotics should be weighed against the potential risks, including adverse effects and promotion of bacterial resistance. For most individuals with travelers' diarrhea, we suggest not treating with antibiotics (Grade 2B). Antibiotic therapy is appropriate for travelers with severe diarrhea characterized by fever and blood, pus, or mucus in the stool, or diarrhea of any severity that substantially interferes with the purpose of travel. (See 'Indications' above.)
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For patients who warrant empiric antibiotic therapy for travelers' diarrhea, we suggest azithromycin or a fluoroquinolone (Grade 2B). Azithromycin is preferred for patients with fever or dysentery (bloody or mucoid diarrhea), children, pregnant women, and travelers to Asia. Rifaximin and rifamycin are alternative agents, but should be avoided in patients with features of invasive diarrhea (eg, bloody or mucoid stool) (See 'Selection' above.)
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Non-antibiotic symptomatic management (eg, bismuth or antimotility agents such as loperamide or diphenoxylate) can be used for mild or moderate diarrhea. For travelers with
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Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment - UpToDate
severe diarrhea, we suggest that antimotility agents only be taken in conjunction with antibiotics (Grade 2C). Because they address the symptoms but not the cause, antimotility agents can mask the amount of fluid lost into the intestine. Additionally, there is concern that they can prolong or exacerbate dysentery. These agents should be discontinued promptly if abdominal pain develops, other symptoms worsen, or diarrhea persists. (See 'Symptomatic therapy' above.) ●
For patients with diarrhea that has persisted for more than 10 to 14 days or for those whose diarrhea does not improve with antibiotic therapy, less common or drug-resistant pathogens may be causative. For such patients, evaluation focuses on identifying the infecting pathogen so that therapy can be targeted. In addition to a stool culture, this includes examination of stool for ova and parasites. (See 'Patients with persistent diarrhea' above.)
ACKNOWLEDGMENT The editorial staff at UpToDate would like to acknowledge Christine A Wanke, MD, who contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES 1. Greenwood Z, Black J, Weld L, et al. Gastrointestinal infection among international travelers globally. J Travel Med 2008; 15:221. 2. Steffen R, Hill DR, DuPont HL. Traveler's diarrhea: a clinical review. JAMA 2015; 313:71. 3. Hill DR. Health problems in a large cohort of Americans traveling to developing countries. J Travel Med 2000; 7:259. 4. Stoney RJ, Han PV, Barnett ED, et al. Travelers' Diarrhea and Other Gastrointestinal Symptoms Among Boston-Area International Travelers. Am J Trop Med Hyg 2017; 96:1388. 5. Arcilla MS, van Hattem JM, Haverkate MR, et al. Import and spread of extended-spectrum βlactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study. Lancet Infect Dis 2017; 17:78. 6. Reuland EA, Sonder GJ, Stolte I, et al. Travel to Asia and traveller's diarrhoea with antibiotic treatment are independent risk factors for acquiring ciprofloxacin-resistant and extended spectrum β-lactamase-producing Enterobacteriaceae-a prospective cohort study. Clin Microbiol Infect 2016; 22:731.e1. https://www.uptodate.com/contents/travelers-diarrhea-clinical-manifestations-diagnosis-and-treatment/print?search=diarreia cronica paises rec…
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7. Lübbert C, Straube L, Stein C, et al. Colonization with extended-spectrum beta-lactamaseproducing and carbapenemase-producing Enterobacteriaceae in international travelers returning to Germany. Int J Med Microbiol 2015; 305:148. 8. Kantele A, Lääveri T, Mero S, et al. Antimicrobials increase travelers' risk of colonization by extended-spectrum betalactamase-producing Enterobacteriaceae. Clin Infect Dis 2015; 60:837. 9. Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med 2017; 24:S57. 10. von Sonnenburg F, Tornieporth N, Waiyaki P, et al. Risk and aetiology of diarrhoea at various tourist destinations. Lancet 2000; 356:133. 11. Soonawala D, Vlot JA, Visser LG. Inconvenience due to travelers' diarrhea: a prospective follow-up study. BMC Infect Dis 2011; 11:322. 12. Steffen R, Collard F, Tornieporth N, et al. Epidemiology, etiology, and impact of traveler's diarrhea in Jamaica. JAMA 1999; 281:811. 13. Rendi-Wagner P, Kollaritsch H. Drug prophylaxis for travelers' diarrhea. Clin Infect Dis 2002; 34:628. 14. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis 2017; 65:e45. 15. Antikainen J, Kantele A, Pakkanen SH, et al. A quantitative polymerase chain reaction assay for rapid detection of 9 pathogens directly from stools of travelers with diarrhea. Clin Gastroenterol Hepatol 2013; 11:1300. 16. Avery ME, Snyder JD. Oral therapy for acute diarrhea. The underused simple solution. N Engl J Med 1990; 323:891. 17. Carpenter CC, Greenough WB, Pierce NF. Oral-rehydration therapy--the role of polymeric substrates. N Engl J Med 1988; 319:1346. 18. Caeiro JP, DuPont HL, Albrecht H, Ericsson CD. Oral rehydration therapy plus loperamide versus loperamide alone in the treatment of traveler's diarrhea. Clin Infect Dis 1999; 28:1286. 19. de Zoysa I, Kirkwood B, Feachem R, Lindsay-Smith E. Preparation of sugar-salt solutions. Trans R Soc Trop Med Hyg 1984; 78:260.
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20. Huang DB, Awasthi M, Le BM, et al. The role of diet in the treatment of travelers' diarrhea: a pilot study. Clin Infect Dis 2004; 39:468. 21. Kuschner RA, Trofa AF, Thomas RJ, et al. Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent. Clin Infect Dis 1995; 21:536. 22. Murray BE. Resistance of Shigella, Salmonella, and other selected enteric pathogens to antimicrobial agents. Rev Infect Dis 1986; 8 Suppl 2:S172. 23. Murray BE, Mathewson JJ, DuPont HL, et al. Emergence of resistant fecal Escherichia coli in travelers not taking prophylactic antimicrobial agents. Antimicrob Agents Chemother 1990; 34:515. 24. Adachi JA, Ericsson CD, Jiang ZD, et al. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis 2003; 37:1165. 25. Sanders JW, Frenck RW, Putnam SD, et al. Azithromycin and loperamide are comparable to levofloxacin and loperamide for the treatment of traveler's diarrhea in United States military personnel in Turkey. Clin Infect Dis 2007; 45:294. 26. Tribble DR, Sanders JW, Pang LW, et al. Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3day levofloxacin regimen. Clin Infect Dis 2007; 44:338. 27. Riddle MS, Connor P, Fraser J, et al. Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide. Clin Infect Dis 2017; 65:2008. 28. Steffen R. Epidemiologic studies of travelers' diarrhea, severe gastrointestinal infections, and cholera. Rev Infect Dis 1986; 8 Suppl 2:S122. 29. From the Centers for Disease Control. Cholera--international travel, 1992. JAMA 1992; 268:1648. 30. Smith KE, Besser JM, Hedberg CW, et al. Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998. Investigation Team. N Engl J Med 1999; 340:1525. 31. Hakanen A, Jousimies-Somer H, Siitonen A, et al. Fluoroquinolone resistance in Campylobacter jejuni isolates in travelers returning to Finland: association of ciprofloxacin resistance to travel destination. Emerg Infect Dis 2003; 9:267.
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32. Nachamkin I, Ung H, Li M. Increasing fluoroquinolone resistance in Campylobacter jejuni, Pennsylvania, USA,1982-2001. Emerg Infect Dis 2002; 8:1501. 33. Sanders JW, Isenbarger DW, Walz SE, et al. An observational clinic-based study of diarrheal illness in deployed United States military personnel in Thailand: presentation and outcome of Campylobacter infection. Am J Trop Med Hyg 2002; 67:533. 34. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med 2006; 355:2452. 35. US Food and Drug Administration. FDA Drug Safety Communication: FDA updates and war nings for oral and injectable fluoroquinolone antibiotics due to disabling side effects, 2016. ht tps://www.fda.gov/downloads/Drugs/DrugSafety/UCM513019.pdf (Accessed on November 1 5, 2017). 36. DuPont HL, Ericsson CD. Prevention and treatment of traveler's diarrhea. N Engl J Med 1993; 328:1821. 37. Mattila L, Peltola H, Siitonen A, et al. Short-term treatment of traveler's diarrhea with norfloxacin: a double-blind, placebo-controlled study during two seasons. Clin Infect Dis 1993; 17:779. 38. Taylor DN, Sanchez JL, Candler W, et al. Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial. Ann Intern Med 1991; 114:731. 39. Pichler HE, Diridl G, Stickler K, Wolf D. Clinical efficacy of ciprofloxacin compared with placebo in bacterial diarrhea. Am J Med 1987; 82:329. 40. Salam I, Katelaris P, Leigh-Smith S, Farthing MJ. Randomised trial of single-dose ciprofloxacin for travellers' diarrhoea. Lancet 1994; 344:1537. 41. Steffen R, Sack DA, Riopel L, et al. Therapy of travelers' diarrhea with rifaximin on various continents. Am J Gastroenterol 2003; 98:1073. 42. DuPont HL, Jiang ZD, Ericsson CD, et al. Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial. Clin Infect Dis 2001; 33:1807. 43. Adachi JA, DuPont HL. Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. Clin Infect Dis 2006; 42:541. 44. Dupont HL, Jiang ZD, Belkind-Gerson J, et al. Treatment of travelers' diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone. Clin Gastroenterol Hepatol 2007; 5:451.
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45. Study to Evaluate Safety and Efficacy of Rifamycin SV Multi-Matrix System (MMX) for the Tr eatment of Traveler's Diarrhea (TD). ClinicalTrials.gov Identifier: NCT01142089 https://clinica ltrials.gov/ct2/show/results/NCT01142089?view=results. 46. DuPont HL, Hornick RB. Adverse effect of lomotil therapy in shigellosis. JAMA 1973; 226:1525. 47. Petruccelli BP, Murphy GS, Sanchez JL, et al. Treatment of traveler's diarrhea with ciprofloxacin and loperamide. J Infect Dis 1992; 165:557. 48. Riddle MS, Arnold S, Tribble DR. Effect of adjunctive loperamide in combination with antibiotics on treatment outcomes in traveler's diarrhea: a systematic review and metaanalysis. Clin Infect Dis 2008; 47:1007. 49. Swaminathan A, Torresi J, Schlagenhauf P, et al. A global study of pathogens and host risk factors associated with infectious gastrointestinal disease in returned international travellers. J Infect 2009; 59:19. 50. Ross AG, Olds GR, Cripps AW, et al. Enteropathogens and chronic illness in returning travelers. N Engl J Med 2013; 368:1817.
Topic 99648 Version 16.0
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GRAPHICS Oral agents for self-treatment of travelers' diarrhea in adults Agent Azithromycin
Dose 1000 mg once
500 mg once daily
Duration Single dose*
Comment
Preferred for dysentery or febrile diarrhea, travelers from Southeast Asia, and pregnant women
Three-day course
The 1000 mg dose may be associated with nausea Levofloxacin
500 mg once daily
Single dose* or three-day course
Ciprofloxacin
750 mg once
Single dose*
500 mg twice daily
Three-day course
Ofloxacin
400 mg once daily
Single dose* or three-day course
Rifaximin
200 mg three times daily
Three-day course
Rifamycin
Two (194 mg) tablets twice daily
Three-day course
Fluoroquinolones are associated with multiple adverse events
Not for use with dysentery or febrile diarrhea
* If symptoms have not resolved after 24 hours, the regimen can be extended to complete a three-day course (using the dosing listed for the three-day course). Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers' diarrhea: a graded expert panel report. J Travel Med 2017; 24:S57. Graphic 75355 Version 8.0
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Contributor Disclosures Regina LaRocque, MD, MPH Nothing to disclose Jason B Harris, MD, MPH Consultant/Advisory Boards: Scientific Advisory Committee [Cholera (Oral cholera vaccine)]. Stephen B Calderwood, MD Consultant/Advisory Boards: Day Zero Diagnostics [Whole genome sequencing for microbial identification and determination of antimicrobial susceptibility]. Equity Ownership: Pulmatrix [Infectious diseases (Inhaled antimicrobials)]. Allyson Bloom, MD Nothing to disclose Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy
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