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• Section 2 - Yellow Fever Vaccine & Malaria Prevention Information, by Country
• Section 2 - Perspectives : Antibiotics in Travelers' Diarrhea - Balancing Benefit & Risk

Travelers’ Diarrhea

Cdc yellow book 2024.

Author(s): Bradley Connor

Infectious Agents

Risk for travelers, clinical presentation.

Travelers’ diarrhea (TD) is the most predictable travel-related illness. Attack rates range from 30%–70% of travelers during a 2-week period, depending on the destination and season of travel. Traditionally, TD was thought to be prevented by following simple dietary recommendations (e.g., “boil it, cook it, peel it, or forget it”), but studies have found that people who follow these rules can still become ill. Poor hygiene practices in local restaurants and underlying hygiene and sanitation infrastructure deficiencies are likely the largest contributors to the risk for TD.

TD is a clinical syndrome that can result from a variety of intestinal pathogens. Bacteria are the predominant enteropathogens and are thought to account for ≥80%–90% of cases. Intestinal viruses account for at least 5%–15% of illnesses, although the use of multiplex molecular diagnostic assays demonstrates that their contribution to the overall burden of TD disease is probably greater than previously estimated. Infections with protozoal pathogens are slower to manifest symptoms and collectively account for ≈10% of diagnoses in longer-term travelers (see Sec. 11, Ch. 7, Persistent Diarrhea in Returned Travelers ).

What is commonly known as “food poisoning” involves the ingestion of infectious agents that release toxins (e.g., Clostridium perfringens ) or consumption of preformed toxins (e.g., Staphylococcal food poisoning). In toxin-mediated illness, both vomiting and diarrhea can be present; symptoms usually resolve spontaneously within 12–24 hours.

Bacteria are the most common cause of TD. Overall, the most common pathogen identified is enterotoxigenic Escherichia coli , followed by Campylobacter jejuni , Shigella spp., and Salmonella spp. Enteroaggregative and other E. coli pathotypes also are commonly found in cases of TD. Surveillance also points to Aeromonas spp., Plesiomonas spp., and newly recognized pathogens ( Acrobacter , enterotoxigenic Bacteroides fragilis, Larobacter ) as potential causes of TD.

Viral diarrhea can be caused by several pathogens, including astrovirus, norovirus, and rotavirus.

Protozoal Parasites

Giardia is the main protozoal pathogen found in TD. Entamoeba histolytica and Cryptosporidium are relatively uncommon causes of TD. The risk for Cyclospora is highly geographic and seasonal: the most well-known risks are in Guatemala, Haiti, Nepal, and Peru. Dientamoeba fragilis is a flagellate occasionally associated with diarrhea in travelers. Several pathogens are discussed in their own chapters in Section 5.

TD occurs equally in male and female travelers; it is more common in young adult travelers than in older travelers. In short-term travelers, bouts of TD do not appear to protect against future attacks, and >1 episode of TD can occur during a single trip. A cohort of expatriates residing in Kathmandu, Nepal, experienced an average of 3.2 episodes of TD per person during their first year. In more temperate regions, seasonal variations in diarrhea risk can occur. In South Asia, for example, much higher TD attack rates are reported during the hot months preceding the monsoon.

Particularly in locations where large numbers of people lack plumbing or latrine access, stool contamination in the environment will be greater and more accessible to disease-transmitting vectors (e.g., flies). Inadequate electrical capacity leading to frequent blackouts or poorly functioning refrigeration can result in unsafe food storage and an additional increased risk for disease. Lack of safe, potable water contributes to food and drink contamination, as do unhealthful shortcuts in cleaning hands, countertops, cutting boards, utensils, and foods (e.g., fruits and vegetables). In some places, handwashing might not be a social norm and could represent an extra expense; thus, adequately equipped handwashing stations might not be available in food preparation areas.

Where provided, effective food handling courses have been shown to decrease the risk for TD. However, even in high-income countries, food handling and preparation in restaurants has been linked to TD caused by pathogens such as Shigella sonnei .

The incubation period between exposure and clinical presentation can provide clues to etiology. Toxin-mediated illness, for example, generally causes symptoms within a few hours. By contrast, bacterial and viral pathogens have an incubation period of 6–72 hours. In general, protozoal pathogens have longer incubation periods (1–2 weeks), rarely presenting in the first few days of travel. An exception is Cyclospora cayetanensis , which can present quickly in areas of high risk.

Bacterial and viral TD present with the sudden onset of bothersome symptoms that can range from mild cramps and urgent loose stools to severe abdominal pain, bloody diarrhea, fever, and vomiting; with norovirus, vomiting can be more prominent. Diarrhea caused by protozoa (e.g., E. histolytica , Giardia duodenalis ) generally has a more gradual onset of low-grade symptoms, with 2–5 loose stools per day.

Untreated, bacterial diarrhea usually lasts 3–7 days. Viral diarrhea generally lasts 2–3 days. Protozoal diarrhea can persist for weeks to months without treatment. An acute bout of TD can lead to persistent enteric symptoms, even in the absence of continued infection. This presentation is commonly referred to as postinfectious irritable bowel syndrome (see Sec. 11, Ch. 7, Persistent Diarrhea in Returned Travelers ). Other postinfectious sequelae can include reactive arthritis and Guillain-Barré syndrome.

Vaccines are not available in the United States for pathogens that commonly cause TD. Traveler adherence to recommended approaches can, however, help reduce, although never fully eliminate, the risk for illness. These recommendations include making careful food and beverage choices, using agents other than antimicrobial medications for prophylaxis, and carefully washing hands with soap whenever available. When handwashing is not possible, small containers of hand sanitizer containing ≥60% alcohol can make it easier for travelers to clean their hands before eating. Refer to the relevant chapters in Section 5 ( Cholera , Hepatitis A , and Typhoid & Paratyphoid Fever ) for details regarding vaccines to prevent other foodborne and waterborne infections to which travelers are susceptible.

Food & Beverage Selection

Care in selecting food and beverages can help minimize the risk for acquiring TD. See Sec. 2, Ch. 8, Food & Water Precautions , for detailed food and beverage recommendations. Although food and water precautions are recommended, travelers are not always able to adhere to the advice. Furthermore, food safety factors (e.g., restaurant hygiene) are out of the traveler’s control.

Non-Antimicrobial Drugs for Prophylaxis

Bismuth subsalicylate.

The primary agent studied for prevention of TD, other than antibiotics, is bismuth subsalicylate (BSS). Studies from Mexico have shown that this agent reduces the incidence of TD by approximately 50%. BSS commonly causes blackening of the tongue and stool and can cause constipation, nausea, and rarely tinnitus.

Contraindications & Safety

Travelers with aspirin allergy, gout, or renal insufficiency, and those taking anticoagulants, methotrexate, or probenecid should not take BSS. In travelers taking aspirin or salicylates for other reasons, concomitant use of BSS can increase the risk of developing salicylate toxicity.

BSS is not generally recommended for children aged <12 years; some clinicians use it off-label, however, with caution to avoid administering BSS to children aged ≤18 years with viral infections (e.g., influenza, varicella), because of the risk for Reye’s syndrome. BSS is not recommended for children aged <3 years or pregnant people.

Studies have not established the safety of BSS use for >3 weeks. Because of the number of tablets required and the inconvenient dosing, BSS is not commonly used as TD prophylaxis.

Probiotics (e.g., Lactobacillus GG, Saccharomyces boulardii ) have been studied in small numbers of people as TD prevention, but results are inconclusive, partly because standardized preparations of these bacteria are not reliably available. Studies of probiotics to prevent TD are ongoing, but data are insufficient to recommend their use (see the Sec. 2, Ch. 14, Complementary & Integrative Health Approaches to Travel Wellness ).

Anecdotal reports claim beneficial outcomes after using bovine colostrum as a daily prophylaxis agent for TD. However, commercially sold preparations of bovine colostrum marketed as dietary supplements are not approved by the US Food and Drug Administration (FDA). Because no data from rigorous clinical trials demonstrate efficacy, insufficient information is available to recommend the use of bovine colostrum to prevent TD.

Prophylactic Antibiotics

Older controlled studies showed that use of antibiotics reduced diarrhea attack rates by 90%. For most travelers, though, the risks associated with the use of prophylactic antibiotics (see below) do not outweigh the benefits. Prophylactic antibiotics might rarely be considered for short-term travelers who are high-risk hosts (e.g., immunocompromised people or people who have significant medical comorbidities).

The prophylactic antibiotic of choice has changed over the past few decades as resistance patterns have evolved. Historically, fluoroquinolones have been the most effective antibiotics for prophylaxis and treatment of bacterial TD pathogens, but resistance among Campylobacter and Shigella species globally now limits their use. In addition, fluoroquinolones are associated with tendinitis, concerns for QT interval prolongation, and an increased risk for Clostridioides difficile infection. Current guidelines discourage their use for prophylaxis. Alternative considerations include rifaximin and rifamycin SV.

Antimicrobial Resistance & Other Adverse Consequences

Prophylactic antibiotics are not recommended for most travelers. Prophylactic antibiotics afford no protection against nonbacterial pathogens and can remove normally protective microflora from the bowel, increasing the risk for infection with resistant bacterial pathogens. Travelers can become colonized with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), a risk that is increased by exposure to antibiotics while abroad (see Sec 2, Ch. 17, . . . perspectives: Antibiotics in Travelers’ Diarrhea—Balancing Benefit & Risk , and Sec. 11, Ch. 5, Antimicrobial Resistance ).

Use of prophylactic antibiotics limits therapeutic options if TD occurs; a traveler relying on prophylactic antibiotics will need to carry an alternative antibiotic to use if severe diarrhea develops. Additionally, use of antibiotics has been associated with allergic and other adverse reactions.

Antibiotics

The effectiveness of a particular antimicrobial drug depends on the etiologic agent and its antibiotic sensitivity ( Table 2-09 ). If tolerated, single-dose regimens are equivalent to multidose regimens and might be more convenient for the traveler.

Azithromycin

Azithromycin is an alternative to fluoroquinolones (see below), although enteropathogens with decreased azithromycin susceptibility have been documented in several countries. The simplest azithromycin treatment regimen is a single dose of 1,000 mg, but side effects (mainly nausea) can limit the acceptability of this large dose; taking the medication as 2 divided doses on the same day can help.

Fluoroquinolones

Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) have traditionally been the first-line antibiotics for empiric therapy of TD or to treat specific bacterial pathogens. Increasing microbial resistance to fluoroquinolones, however, especially among Campylobacter isolates, limits their usefulness in many destinations, particularly South and Southeast Asia, where both Campylobacter infection and fluoroquinolone resistance are prevalent. Increasing fluoroquinolone resistance has been reported from other destinations and in other bacterial pathogens, including in Salmonella and Shigella . Furthermore, fluoroquinolones now carry a black box warning from the FDA regarding multiple adverse reactions including aortic tears, hypoglycemia, mental health side effects, and tendinitis and tendon rupture.

Rifamycin SV

A new therapeutic option is rifamycin SV, approved by the FDA in November 2018 to treat TD caused by noninvasive strains of E. coli in adults. Rifamycin SV is a nonabsorbable antibiotic in the ansamycin class of antibacterial drugs formulated with an enteric coating that targets delivery of the drug to the distal small bowel and colon. Two randomized clinical trials showed that rifamycin SV was superior to placebo and non-inferior to ciprofloxacin in the treatment of TD. As with rifaximin (see below), travelers would need to carry a separate antibiotic (e.g., azithromycin) in case of infection due to an invasive pathogen.

Rifaximin has been approved to treat TD caused by noninvasive strains of E. coli . Since travelers likely cannot distinguish between invasive and noninvasive diarrhea, however, and since they would have to carry a backup drug in the event of invasive diarrhea, the overall usefulness of rifaximin as empiric self-treatment remains undetermined.

Table 2-09 Acute diarrhea antibiotic treatment recommendations 1

ANTIBIOTIC 1

Azithromycin 2,3

Single or divided dose 4

Ciprofloxacin

Single dose 4

Levofloxacin

1–3 days 4

Rifamycin SV 5

Rifaximin 5

Abbreviations: BID, twice daily; QD, once daily; TID, three times a day

1 Antibiotic regimens can be combined with loperamide 4 mg, initially, followed by 2 mg after each loose stool, not to exceed 16 mg in a 24- hour period.

2 Use empirically as first-line treatment for travelers’ diarrhea in Southeast Asia or other areas if fluoroquinolone- resistant bacteria are suspected.

3 Preferred treatment for dysentery or febrile diarrhea.

4 If symptoms are not resolved after 24 hours, continue daily dosing for up to 3 days.

5 Do not use if clinical suspicion for Campylobacter , Salmonella , Shigella , or other causes of invasive diarrhea. Use may be reserved for patients unable to receive azithromycin or fluoroquinolones.

Antibiotics are effective in reducing the duration of diarrhea by ≈1–2 days in cases caused by bacterial pathogens susceptible to the antibiotic prescribed. However, concerns about the adverse consequences of using antibiotics to treat TD remain. Travelers who take antibiotics are at risk of becoming colonized by drug-resistant organisms (e.g., ESBL-PE), resulting in potential harm to travelers—particularly immunocompromised people and people prone to urinary tract infections—and the possibility of introducing resistant bacteria into the community.

In addition, antibiotic use can affect the travelers’ own microbiota and increase the potential for C. difficile infection. These concerns must be weighed against the consequences of TD and the role of antibiotics in shortening the acute illness and possibly preventing postinfectious sequelae. Primarily because of these concerns, an expert advisory panel was convened in 2016 to prepare consensus guidelines on the prevention and treatment of TD. The advisory panel suggested a classification of TD using functional impact for defining severity ( Box 2-03 ) rather than the frequency-based algorithm used traditionally. The guidelines suggest an approach that matches therapeutic intervention with severity of illness, in terms of both safety and effectiveness ( Box 2-04 ).

Box 2-03 Acute travelers’ diarrhea: functional definitions

Mild diarrhea.

Tolerable, not distressing, does not interfere with planned activities

MODERATE DIARRHEA

Distressing or interferes with planned activities

SEVERE DIARRHEA

Incapacitating or completely prevents planned activities

All dysentery is considered severe

Box 2-04 Acute travelers’ diarrhea: treatment recommendations

Antibiotic treatment not recommended

Consider treatment with bismuth subsalicylate or loperamide

Antibiotics can be used for treatment

• Azithromycin

• Fluoroquinolones

• Rifaximin (for moderate, noninvasive diarrhea)

Antimotility drugs

• Consider loperamide for use as monotherapy or as adjunctive therapy

Antibiotic treatment is advised (single-dose regimens may be used)

• Azithromycin is preferred

• Fluoroquinolones or rifaximin1 can be used for severe, non-dysenteric diarrhea

• Consider loperamide for use as adjunctive therapy

• Not recommended as monotherapy for patients with bloody diarrhea or diarrhea and fever

Antimotility Agents

Antimotility agents provide symptomatic relief and are useful therapy in TD. Synthetic opiates (e.g., diphenoxylate, loperamide) can reduce frequency of bowel movements and therefore enable travelers to ride on an airplane or bus. Loperamide appears to have antisecretory properties as well. The safety of loperamide when used along with an antibiotic has been well established, even in cases of invasive pathogens; however, acquisition of ESBL-PE might be more common when loperamide and antibiotics are coadministered.

Antimotility agents alone are not recommended for patients with bloody diarrhea or those who have diarrhea and fever. Loperamide can be used in children, and liquid formulations are available. In practice, however, these drugs are rarely given to children aged <6 years.

Oral Rehydration Therapy

Fluids and electrolytes are lost during TD, and replenishment is important, especially in young children, older adults, and adults with chronic medical illness. In otherwise healthy adult travelers, severe dehydration from TD is unusual unless vomiting is prolonged. Nonetheless, replacement of fluid losses is key to diarrhea therapy and helps the traveler feel better more quickly. Travelers should remember to use only beverages that are sealed, treated with chlorine, boiled, or are otherwise known to be purified (see Sec. 2, Ch. 9, Water Disinfection ).

For severe fluid loss, replacement is best accomplished with oral rehydration solution (ORS) prepared from packaged oral rehydration salts (e.g., those provided by the World Health Organization). ORS is widely available at stores and pharmacies in most low- and middle-income countries. ORS is prepared by adding 1 packet to the indicated volume of boiled or treated water—generally 1 liter. Due to their saltiness, travelers might find most ORS formulations relatively unpalatable. In mild cases, rehydration can be maintained with any preferred liquid (including sports drinks), although overly sweet drinks (e.g., sodas) can cause osmotic diarrhea if consumed in quantity.

Travelers’ Diarrhea Caused by Protozoa

The most common parasitic cause of TD is Giardia duodenalis , and treatment options include metronidazole, nitazoxanide, and tinidazole (see Sec. 5, Part 3, Ch.12, Giardiasis ). Amebiasis (see Sec. 5, Part 3, Ch. 1, Amebiasis ) should be treated with metronidazole or tinidazole, then treated with a luminal agent (e.g., iodoquinol or paromomycin). Although cryptosporidiosis is usually a self-limited illness in immunocompetent people, clinicians can consider nitazoxanide as a treatment option (see Sec. 5, Part 3, Ch. 3, Cryptosporidiosis ). Cyclosporiasis should be treated with trimethoprim-sulfamethoxazole but not trimethoprim alone (see Sec. 5, Part 3, Ch. 5, Cyclosporiasis ).

Travelers’ Diarrhea in Children

Children who accompany their parents on trips to high-risk destinations can contract TD, and their risk is elevated if they are visiting friends and family. Causative organisms include bacteria responsible for TD in adults, as well as viruses (e.g., norovirus, rotavirus). The main treatment for TD in children is ORS. Infants and younger children with TD are at greater risk for dehydration, which is best prevented by the early initiation of oral rehydration.

Consider recommending empiric antibiotic therapy for bloody or severe watery diarrhea or evidence of systemic infection. In older children and teenagers, treatment guidelines follow those for adults, with possible adjustments in the dose of medication. Among younger children, macrolides (e.g., azithromycin) are considered first-line antibiotic therapy. Rifaximin is approved for use in children aged ≥12 years. Rifamycin SV is approved for use only in adults.

Breastfed infants should continue to nurse on demand, and bottle-fed infants can continue to drink formula. Older infants and children should be encouraged to eat and should consume a regular diet. Children in diapers are at risk for developing diaper rash on their buttocks in response to liquid stool. Barrier creams (e.g., zinc oxide, petrolatum) could be applied at the onset of diarrhea to help prevent and treat rash; hydrocortisone cream is the best treatment for an established rash. More information about diarrhea and dehydration is discussed in Sec. 7, Ch. 3, Traveling Safely with Infants & Children .

The following authors contributed to the previous version of this chapter: Bradley A. Connor

Bibliography

Black RE. Epidemiology of travelers’ diarrhea and relative importance of various pathogens. Rev Infect Dis. 1990;12(Suppl 1):S73–9.

DeBruyn G, Hahn S, Borwick A. Antibiotic treatment for travelers’ diarrhea. Cochrane Database Syst Rev. 2000;3:1–21.

Eckbo EJ, Yansouni CP, Pernica JM, Goldfarb DM. New tools to test stool: managing travelers’ diarrhea in the era of molecular diagnostics. Infect Dis Clin N Am. 2019;33(1):197–212.

Kantele A, Lääveri T, Mero S, Vilkman K, Pakkanen S, Ollgren J, et al. Antimicrobials increase travelers’ risk of colonization by extended-spectrum beta lactamase producing Enterobacteriaceae. Clin Infect Dis. 2015;60(6):837–46.

Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB, Shiferaw B, et al. Travel-associated enteric infections diagnosed after return to the United States, Foodborne Diseases Active Surveillance Network (FoodNet), 2004–2009. Clin Infect Dis. 2012;54(Suppl 5):S480–7.

McFarland LV. Meta-analysis of probiotics for the prevention of travelers’ diarrhea. Travel Med Infect Dis. 2007;5(2):97–105.

Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky PE, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. J Travel Med. 2017;24(Suppl 1):S2–19.

Riddle MS, DuPont HL, Connor BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111(5):602–22.

Schaumburg F, Correa-Martinez CL, Niemann S, Köck R, Becker K. Aetiology of traveller’s diarrhea: a nested case-control study. Travel Med Infect Dis. 2020;37:101696.

Schaumburg F, Sertic SM, Correa-Martinez C, Mellmann A, Kock R, Becker K. Acquisition and colonization dynamics of antimicrobial-resistant bacteria during international travel: a prospective cohort study. Clin Microbiol Infect. 2019;25(10):e1–1287.e7.

Shlim DR. Looking for evidence that personal hygiene precautions prevent travelers’ diarrhea. Clin Infect Dis. 2005;41(Suppl 8):S531–5.

Steffen R, Hill DR, DuPont HL. Traveler’s diarrhea: a clinical review. JAMA. 2015;313(1):71–80.

Youmans BP, et al. Characterization of the human gut microbiome during travelers’ diarrhea. Gut Microbes. 2015;6(2):110–9.

Zboromyrska Y, Hurtado JC, Salvador P, Alvarez-Martinez MJ, Valls ME, Marcos MA, et al. Aetiology of travelers’ diarrhea: evaluation of a multiplex PCR tool to detect different enteropathogens. Clin Microbiol Infect. 2014;20:O753–9.

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Volume 44, Issue 1, January-February 2015

Advising travellers about management of travellers’ diarrhoea

How is td defined.

Classic, severe TD is usually defined as at least three unformed bowel movements occurring within a 24-hour period, often accompanied by cramps, nausea, vomiting, fever and/or blood in the stools. 5–7 Moderate TD is defined as one or two unformed bowel movements and other symptoms occurring every 24 hours or as three or more unformed bowel movements without additional symptoms. Mild TD is defined as one or two unformed bowel movements without any additional symptoms and without interference with daily activities. 8,9 TD generally resolves spontaneously, usually after 3–4 days, 8 but, in the interim, frequently leads to disruption of planned activities.

What are the causes of TD?

Approximately 50–80% of TD is caused by bacterial infections; enterotoxigenic Escherichia coli (ETEC) is the most common cause overall. Other bacterial causes include enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), Shigella , Campylobacter and Salmonella species. The exact breakdown of organisms varies according to destination, season and other factors. Noroviruses cause 10–20% of TD cases. Protozoal parasites should be considered particularly in those with persistent diarrhoea (illness lasting ≥14 days) or when antibacterial therapy fails to shorten illness. 10

How can TD be prevented?

Methods for preventing TD include avoidance, immunisation, non-antibiotic interventions or antibiotic prophylaxis. 11

What avoidance measures are generally recommended and do they work?

Avoidance of TD has traditionally relied on recommendations regarding careful food and drink choices (avoiding untreated/unboiled tap water, including ice and water used for brushing teeth, and raw foods such as salads, uncooked vegetables or fruits that cannot be peeled). This underpins the saying ‘Boil it, cook it, peel it or forget it…. easy to remember, impossible to do’. Additional standard advice is that undercooked or raw meat, fish and shellfish are high-risk foods. However, whether deliberately or inadvertently, most people find it very difficult to adhere to dietary restrictions 12 and over 95% of people disobey the rules of ‘safe’ eating and drinking within a few days of leaving home. Additionally, there is minimal evidence for a correlation between adherence to dietary precautions and a reduced risk of TD, 13 although common sense nevertheless supports care with food selection. 4

Where people eat may be more important than what people eat. Risks are associated, in descending order, with street vendors, restaurants and private homes. Use of antibacterial handwash before eating is also recommended. 14

Which vaccines can be considered?

Immunisation has little practical role in the prevention of TD and the only potentially relevant vaccines are those against rotavirus (infants only) and the oral cholera vaccine.

The cholera vaccine has >90% efficacy for prevention of Vibrio cholera but travellers are rarely at risk of infection with this pathogen. 1 The vaccine contains a recombinant B subunit of the cholera toxin that is antigenically similar to the heat-labile toxin of ETEC; therefore, the cholera vaccine may also reduce ETEC TD. However, it is not licensed for TD prevention in Australia and, although initially thought to offer a 15–20% short-term (3 months) reduction in TD, a recent Cochrane review showed no statistically significant effects on ETEC diarrhoea or all-cause diarrhoea. 15 Overall, there is, therefore, insufficient evidence to support general use of the cholera vaccine for TD protection, but it may still be considered for individuals with increased risk of severe or complicated TD (eg immunosuppressed or underlying inflammatory bowel disease).

Other vaccines directed against organisms spread by the faecal–oral route are the vaccines for typhoid, hepatitis A and polio, but infection with these organisms rarely causes TD. 15

Do non-antibiotic interventions work?

Several probiotic agents have been studied for treatment and prevention of TD, including Lactobacillus and Saccharomyces preparations. However, their effectiveness for TD prevention has been limited, 11,16,17 and a consensus group has recommended against their use. 4 Other over-the-counter agents are also available (eg travelan, which contains bovine colostrum harvested from cows immunised with an ETEC vaccine) but data regarding overall efficacy of reducing all-cause TD are currently lacking.

Should antibiotic prophylaxis against TD be given?

Quinolone antibiotics are highly effective (80–95%) in preventing TD, but antibiotic prophylaxis is rarely indicated. 4 It may result in a false sense of security and hence less caution in dietary choices, it poses risks of side effects, diarrhoea associated with Clostridium difficile , and, more importantly, would lead to a vast amount of antibiotic use, thus predisposing to more rapid development of antibiotic resistance globally. 11 Therefore non-antibiotic options for prevention and a focus instead on empirical self-treatment if needed according to symptoms are the mainstay of management, aligning with the antimicrobial stewardship perspective of minimisation of antimicrobial overuse and reducing promotion of antimicrobial resistance.

In rare circumstances, it may be reasonable to consider short courses of antibiotic prophylaxis in individuals at very high risk of infection (eg severely immunocompromised). 11 Globally, one of the most commonly used agents in this regard is rifaximin, a non-absorbed semisynthetic rifamycin derivative, which has been shown to be effective and is approved for use for TD prevention in some countries, but it is not approved for this indication in Australia. Other options include the antibiotics discussed below for TD self-treatment.

How should self-treatment of TD be managed?

Because of the limitations of TD prevention measures, the pre-travel consultation should be viewed as an opportunity to ‘arm’ travellers with the knowledge and medication needed to appropriately self-treat, should TD occur during their trip.

The first goal of therapy is the prevention and treatment of dehydration, which is of particular concern for young children, pregnant women and the elderly. Commercial packets of oral rehydration salts are readily available in pharmacies and should be purchased before travel. The other element of TD self-treatment is to recommend travellers bring an antimotility agent plus an antibiotic with them. Loperamide is preferred over the diphenoxylate/atropine combination, as the latter agent is generally less effective and associated with a greater potential for adverse effects.

When should loperamide alone versus loperamide plus an antibiotic be taken?

For mild symptoms of watery diarrhoea, self-treatment with oral rehydration plus loperamide is recommended. Loperamide therapy alone has no untoward effects in mild TD 18 but if symptoms worsen, or do not improve after 24 hours, antibiotics should be added. If TD is moderate or severe at onset, then combination therapy with loperamide plus antibiotics should be started immediately, as this optimises the clinical benefit of self-treatment by providing more rapid relief and shortening the symptom duration. 10,19

The recommended dose of loperamide is two tablets (4 mg) stat, then one tablet after each bowel motion to a maximum of eight per 24-hour period until the TD has resolved. Despite warnings regarding the safety of antidiarrhoeal agents with bloody diarrhoea or diarrhoea accompanied by fever, the combination with antibiotics is likely to be safe in the setting of mild febrile dysentery, 18 and a number of studies have shown the combination to be more efficacious than use of either agent alone. 7,18–20 Rapid institution of effective treatment shortens symptoms to 30 hours or less in most people. 12 For example, the duration of diarrhoea was significantly ( P = 0.0002) shorter following treatment with azithromycin plus loperamide (11 h) than with azithromycin alone (34 h). 19

Which antibiotic should be recommended for empirical elf-treatment of TD?

The most commonly used antibiotics for empirical TD therapy are fluoroquinolones (either norfloxacin or ciprofloxacin) or azithromycin ( Table 1 ). Cotrimoxazole has been used but is no longer recommended because of widespread resistance. For TD caused by ETEC, the fluoroquinolones and azithromycin have similar efficacy; however, in Asia (particularly South and South-East Asia), Campylobacter is a common cause of TD and strains occurring in this part of the world show a high degree of resistance to fluoroquinolones. 10,21 Therefore, azithromycin is preferred for travellers to this region. Azithromycin remains generally efficacious despite emerging resistance, and is also the preferred treatment for diarrhoea with complications of dysentery or high fever, and for use in pregnant women or children under the age of 8 years, in whom avoidance of quinolones is preferred. Moreover, the 24-hour dosing of azithromycin may be preferable to the 12-hourly dosing schedule required with fluoroquinolones.

What is the optimal dosing schedule?

The fluoroquinolones and azithromycin have been administered as a single dose or for 3 days ( Table 1 ). Usually a single dose is adequate and there is no apparent clinically important difference in efficacy with either dosing schedule for TD. 10 However, for bacteria such as Campylobacter and Shigella dysenteriae , single-dose therapy may be inadequate. 11 It is reasonable, therefore, to give travellers a 3-day supply of antibiotics and tell them to continue taking the therapy (either 12- or 24-hourly, depending on which antibiotic is prescribed) only if their TD symptoms persist. If the TD has resolved, no further antibiotics need to be taken and any remaining antibiotic doses can be kept in case of a second bout of TD. It is prudent to specifically highlight that this advice differs from the usual instructions to take all tablets even if symptoms have resolved.

What is the optimal empirical TD management in children?

There are few data on empirical treatment of TD in children and limited options for therapy. The mainstay of therapy is oral rehydration solution, particularly for children <6 years of age. Antimotility agents are contraindicated for children because of the increased risk of adverse effects, especially paralytic ileus, toxic megacolon and drowsiness (narcotic effect) with loperamide. 1 The lower age limit recommended for avoiding loperamide varies by location; US guidelines state that loperamide should not be given to infants <2 years of age, the UK <4 years and Australian guidelines state <12 years. 14 However, most Australian practitioners are prepared to use loperamide in children aged 6 years or older, if needed to control symptoms.

A paediatric (powder) formulation of azithromycin is available and is the most commonly recommended agent for children. The usual dose is 10–25 mg/kg for up to 3 days. A practical tip is to ensure that the pharmacy does not reconstitute the powder into a solution, as once dissolved, the solution lasts only for 10 days. Instead, sterile water should be provided along with instructions on how to reconstitute the powder if needed. Fluoroquinolones (ciprofloxacin or norfloxacin 10mg/kg bd) are an alternative option if there are reasons for avoiding azithromycin, with previous concerns regarding potential effects on cartilage not substantiated in recent studies. 14,22

Does starting antibiotics early prevent the chances of developing prolonged symptoms?

Although TD symptoms are short-lived in most cases, 8–15% of affected travellers are symptomatic for more than a week and 2% develop chronic diarrhoea lasting a month or more. 11 Episodes of TD have been shown to be associated with a quintuple risk of developing irritable bowel syndrome (IBS), and post-travel IBS occurs in 3–10% of travellers. However, it is unknown whether IBS can be prevented by starting antimicrobial therapy earlier in the course of enteric infection. 4,18,23

Should tinidazole also be prescribed and, if so, for whom?

Tinidazole can be prescribed as a second antibiotic for empirical self‑treatment as it is effective against the protozoan parasitic enteric pathogen Giardia intestinalis . A dose of 2 g (4 x 500 mg tablets) stat is recommended. However, for most short-term travellers, tinidazole may be unnecessary and the complexity of the additional instructions required may be unwarranted. It is optimally recommended, therefore, for travellers departing on trips of significant duration (>2–3 weeks). If prescribed, the instructions should be to take tinidazole if the TD persists following the 3-day course of antibiotic therapy (fluoroquinolone or azithromycin). This will mean that the TD has lasted for at least 72 hours, thus increasing the likelihood of a parasitic cause.

When should medical care for acute symptoms be recommended?

While most episodes of TD are amenable to self-treatment, if there is a risk of dehydration due to intolerance of oral fluids or comorbidities, as well as in the setting of frank blood in the stool or unremitting fevers (>38.5°C for 48 hours), medical therapy should be sought. 18

How should TD be managed after return?

While a full description of TD management is beyond the scope of this article, for returning travellers with diarrhoea, at least one (preferably three) stool sample(s) should be taken, including specific requests for evaluation of parasites. For patients who are unwell, particularly those with fevers or dysentery, initiation of empirical antibiotic treatment with azithromycin or a quinolone may be needed while awaiting results. For those with prolonged symptoms, tinidazole as empirical therapy for protozoan parasites may be considered. Endoscopic evaluation may also be advisable if no infectious cause is found and symptoms do not resolve.

• Travellers’ diarrhoea continues to affect 20–50% of people undertaking trips to areas with under-developed sanitation and there is minimal evidence for beneficial effects of dietary precautions.
• Evidence for the benefit of cholera vaccine in reducing TD is limited, but it can be considered in people at high risk of infection.
• In 50–80% of TD cases, TD is caused by bacterial infection. Mild diarrhoea can be managed with an antimotility agent (loperamide) alone, but for moderate or severe diarrhoea, early self-treatment with loperamide in conjunction with antibiotics is advised.
• Recommended empirical antibiotics are fluoroquinolones (norfloxacin / ciprofloxacin) or azithromycin for up to 3 days, although in the setting of increasing resistance, the latter is preferred for travellers to South and South-East Asia.

Competing interests: Karin Leader received a consultancy fee from Imuron in relation to the C. difficile vaccine. She is also an ISTM board member and received a consultancy from ISTM to join the GeoSentinel leadership team. She received grants from Sanofi to develop a mobile phone app for splenectomised patients and from GSK to research the use of the HBV vaccine. GSK also paid her to lecture on travel risks at the Asia Pacific Travel Health Conference. She has received support from both GSK and Sanofi to attend travel medicine conferences.

Provenance and peer review: Commissioned, externally peer reviewed

• Diemert DJ. Prevention and self-treatment of travelers’ diarrhea. Prim Care 2002;29:843–55. Search PubMed
• Department of Health and Human Services. Centers for Disease Control and Prevention. Travelers’ Diarrhea. Available at www.cdc.gov/ncidod/dbmd/diseaseinfo/travelersdiarrhea_g.htm [Accessed 25 November 2014]. Search PubMed
• Paredes-Paredes M, Flores-Figueroa J, Dupont HL. Advances in the treatment of travelers’ diarrhea. Curr Gastroenterol Rep 2011;13:402–07. Search PubMed
• DuPont HL, Ericsson CD, Farthing MJ, et al. Expert review of the evidence base for prevention of travelers’ diarrhea. J Travel Med 2009;16:149–60. Search PubMed
• Nair D. Travelers’ diarrhea: prevention, treatment, and post-trip evaluation. J Fam Pract 2013;62:356–61. Search PubMed
• De Bruyn G, Hahn S, Borwick A. Antibiotic treatment for travellers’ diarrhoea. The Cochrane Database Syst Rev 2000:CD002242. Search PubMed
• 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 meta-analysis. Clin Infect Dis 2008;47:1007–14. Search PubMed
• Steffen R. Epidemiology of traveler’s diarrhea. Clin Infect Dis 2005;41(Suppl 8):S536–40. Search PubMed
• Steffen R, Collard F, Tornieporth N, et al. Epidemiology, etiology, and impact of traveler’s diarrhea in Jamaica. JAMA 1999;281:811–17. Search PubMed
• DuPont HL, Ericsson CD, Farthing MJ, et al. Expert review of the evidence base for self-therapy of travelers’ diarrhea. J Travel Med 2009;16:161–71. Search PubMed
• Diemert DJ. Prevention and self-treatment of traveler’s diarrhea. Clin Microbiol Rev 2006;19:583–94. Search PubMed
• Travelers’ diarrhea. NIH Consensus Development Conference. JAMA 1985;253:2700–04. Search PubMed
• Shlim DR. Looking for evidence that personal hygiene precautions prevent traveler’s diarrhea. Clin Infect Dis 2005;41(Suppl 8):S531–35. Search PubMed
• Plourde PJ. Travellers’ diarrhea in children. Paediatr Child Health 2003;8:99–103. Search PubMed
• Ahmed T, Bhuiyan TR, Zaman K, Sinclair D, Qadri F. Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea. Cochrane Database Syst Rev 2013;7:CD009029. Search PubMed
• Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PloS One 2012;7:e34938. Search PubMed
• Centers for Disease Control Prevention. Yellow Book. Chapter 2. Travelers’ Diarrhea. Available at wwwnc.cdc.gov/travel/yellowbook/2014/chapter-2-the-pre-travel-consultation/travelers-diarrhea [Accessed 25 November 2014]. Search PubMed
• Wingate D, Phillips SF, Lewis SJ, et al. Guidelines for adults on self-medication for the treatment of acute diarrhoea. Aliment Pharmacol Ther 2001;15:773–82. Search PubMed
• Ericsson CD, DuPont HL, Okhuysen PC, Jiang ZD, DuPont MW. Loperamide plus azithromycin more effectively treats travelers’ diarrhea in Mexico than azithromycin alone. J Travel Med 2007;14:312–19. Search PubMed
• Murphy GS, Bodhidatta L, Echeverria P, et al. Ciprofloxacin and loperamide in the treatment of bacillary dysentery. Ann Intern Med 1993;118:582–86. Search PubMed
• 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 3-day levofloxacin regimen. Clin Infect Dis 2007;44:338–46. Search PubMed
• Yung A, Leder K, Torresi J, et al. Manual of Travel Medicine. 3rd edn. Melbourne: IP Communciations, 2011. Search PubMed
• Stermer E, Lubezky A, Potasman I, Paster E, Lavy A. Is traveler’s diarrhea a significant risk factor for the development of irritable bowel syndrome? A prospective study. Clin Infect Dis 2006;43:898–901. Search PubMed
• Expert Group for Antibiotic. Antiobiotic: gastrointestinal tract infections: acute gastroenteritis: acute diarrhoea in special groups: travellers’ diarrhoea. In: eTG Complete [Internet] Melbourne. Therapeutic Guidelines Ltd, 2014. Search PubMed

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Printed from Australian Family Physician - https://www.racgp.org.au/afp/2015/january-february/advising-travellers-about-management-of-travellers © The Australian College of General Practitioners www.racgp.org.au

JOHNNIE YATES, M.D.

Am Fam Physician. 2005;71(11):2095-2100

Patient Information: Seen related handout on traveler’s diarrhea , written by the author of this article.

Acute diarrhea affects millions of persons who travel to developing countries each year. Food and water contaminated with fecal matter are the main sources of infection. Bacteria such as enterotoxigenic Escherichia coli , enteroaggregative E. coli , Campylobacter, Salmonella, and Shigella are common causes of traveler’s diarrhea. Parasites and viruses are less common etiologies. Travel destination is the most significant risk factor for traveler’s diarrhea. The efficacy of pretravel counseling and dietary precautions in reducing the incidence of diarrhea is unproven. Empiric treatment of traveler’s diarrhea with antibiotics and loperamide is effective and often limits symptoms to one day. Rifaximin, a recently approved antibiotic, can be used for the treatment of traveler’s diarrhea in regions where noninvasive E. coli is the predominant pathogen. In areas where invasive organisms such as Campylobacter and Shigella are common, fluoroquinolones remain the drug of choice. Azithromycin is recommended in areas with quinolone-resistant Campylobacter and for the treatment of children and pregnant women.

Acute diarrhea is the most common illness among travelers. Up to 55 percent of persons who travel from developed countries to developing countries are affected. 1 , 2 A study 3 of Americans visiting developing countries found that 46 percent acquired diarrhea. The classic definition of traveler’s diarrhea is three or more unformed stools in 24 hours with at least one of the following symptoms: fever, nausea, vomiting, abdominal cramps, tenesmus, or bloody stools. Milder forms can present with fewer than three stools (e.g., an abrupt bout of watery diarrhea with abdominal cramps). Most cases occur within the first two weeks of travel and last about four days without treatment. 1 , 3 Although traveler’s diarrhea rarely is life threatening, it can result in significant morbidity; one in five travelers with diarrhea is bedridden for a day and more than one third have to alter their activities. 1 , 3

Destination is the most significant risk factor for developing traveler’s diarrhea. 1 – 4 Regions with the highest risk are Africa, South Asia, Latin America, and the Middle East. Travelers who are immunocompromised and those with lowered gastric acidity (e.g., patients taking histamineH 2 blockers or proton pump inhibitors) are more susceptible to traveler’s diarrhea. Recently, a genetic susceptibility has been demonstrated. 5 Younger age and adventurous travel increase the risk of developing traveler’s diarrhea, 3 , 6 but persons staying at luxury resorts or on cruise ships also are at risk. 7 , 8

Food and water contaminated with fecal matter are the main reservoirs for the pathogens that cause traveler’s diarrhea. Unsafe foods and beverages include salads, unpeeled fruits, raw or poorly cooked meats and seafood, unpasteurized dairy products, and tap water. Eating in restaurants increases the probability of contracting traveler’s diarrhea 6 and food from street vendors is particularly risky. 9 , 10 Cold sauces, salsas, and foods that are cooked and then reheated also are risky. 6 , 11

In contrast to the largely viral etiology of gastroenteritis in the United States, diarrhea acquired in developing countries is caused mainly by bacteria 1 , 4 , 6 , 12 ( Table 1 ) . Enterotoxigenic Escherichia coli is the pathogen most frequently isolated, but other types of E. coli such as enteroaggregative E. coli have been recognized as common causes of traveler’s diarrhea. 13 Invasive pathogens such as Campylobacter, Shigella, and non-typhoid Salmonella are relatively common depending on the region, while Aeromonas and non-cholera Vibrio species are encountered less frequently.

Protozoal parasites such as Giardia lamblia , Entamoeba histolytica , and Cyclospora cayetanensis are uncommon causes of traveler’s diarrhea, but increase in importance when diarrhea lasts for more than two weeks. 14 Parasites are diagnosed more frequently in returning travelers because of longer incubation periods (often one to two weeks) and because bacterial pathogens may have been treated with antibiotics. Rotavirus and noroviruses are infrequent causes of traveler’s diarrhea, although noroviruses have been responsible for outbreaks on cruise ships.

The prevalence of specific organisms varies with travel destination. 1 , 4 , 12 , 13 , 15 Available data suggest that E. coli is the predominant cause of traveler’s diarrhea in Latin America, the Caribbean, and Africa, while invasive pathogens are relatively uncommon. Enterotoxigenic E. coli and enteroaggregative E. coli may be responsible for up to 71 percent of cases of traveler’s diarrhea in Mexico. 13 In contrast, Campylobacter is a leading cause of traveler’s diarrhea in Thailand 15 – 17 and also is common in Nepal. 6 Regional variation also exists with parasitic causes of traveler’s diarrhea ( Table 2 ) . 12 , 13 For example, Cyclospora is endemic in Nepal, Peru, and Haiti.

Food poisoning is part of the differential diagnosis of traveler’s diarrhea. Gastroenteritis from preformed toxins (e.g., Staphylococcus aureus , Bacillus cereus ) is characterized by a short incubation period (one to six hours), and symptoms typically resolve within 24 hours. 18 Seafood ingestion syndromes such as diarrhetic shellfish poisoning, ciguatera poisoning, and scombroid poisoning also can cause diarrhea in travelers. These syndromes can be distinguished from traveler’s diarrhea by symptoms such as perioral numbness and reversal of temperature sensation (ciguatera poisoning) or flushing and warmth (scombroid poisoning). 19

Although travelers often are advised to “Boil it, cook it, peel it, or forget it,” data on the effectiveness of dietary precautions in preventing traveler’s diarrhea are inconclusive. 3 , 6 , 20 Many travelers find it difficult to adhere to dietary recommendations. 21 In a study 3 of American travelers, nearly one half developed diarrhea despite pretravel advice on avoidance measures; even persons who strictly followed dietary recommendations developed diarrhea. Avoiding high-risk foods and adventuresome eating behaviors may reduce the inoculum of ingested pathogens or prevent the development of other enteric diseases such as typhoid and hepatitis A and E.

Boiling is the best way to purify water. Iodination or chlorination is acceptable but does not kill Cryptosporidium or Cyclospora, and increased contact time is required to kill Giardia in cold or turbid water. 22 Filters with iodine resins generally are effective in purifying water, although it is uncertain whether the contact time with the resin is sufficient to kill viruses. Bottled water generally is safe if the cap and seal are intact.

DRUG PROPHYLAXIS

Antibiotic prophylaxis is not recommended by the Centers for Disease Control and Prevention (CDC) even for high-risk travelers because it can lead to drug-resistant organisms and may give travelers a false sense of security. Although antibiotic prophylaxis does not prevent viral or parasitic infection, some health care professionals believe that it may be an option for travelers who are at high risk of developing traveler’s diarrhea and related complications (e.g., immunocompromised persons). Prophylaxis with fluoroquinolones is up to 90 percent effective. 23 Rifaximin (Xifaxan) may prove to be the preferred antibiotic because it is not absorbed and is well tolerated, although data on its effectiveness for prophylaxis have not yet been published.

Bismuth subsalicylate (Pepto-Bismol) provides a rate of protection of about 60 percent against traveler’s diarrhea. 24 However, it is not recommended for persons taking anticoagulants or other salicylates. Because bismuth subsalicylate interferes with the absorption of doxycycline (Vibramycin), it should not be taken by travelers using doxycycline for malaria prophylaxis. Travelers should be warned about possible reversible side effects of bismuth subsalicylate, such as a black tongue, dark stools, and tinnitus.

Probiotics are a more natural approach to prophylaxis of traveler’s diarrhea. Probiotics colonize the gastrointestinal tract and theoretically prevent pathogenic organisms from infecting the gut. Studies 25 , 26 of Lactobacillus GG (Culturelle) have suggested protection rates of up to 47 percent. More studies are needed to confirm the efficacy of probiotic prophylaxis. Agents for the prophylaxis of traveler’s diarrhea are summarized in Table 3 .

Empiric Treatment

Counseling travelers about food precautions does not eliminate the risk of traveler’s diarrhea, and nonantibiotic prophylaxis requires frequent dosing to achieve only a modest reduction in risk. In addition, the traveler with diarrhea may have difficulty accessing medical care, the quality of care may be poor, and the quality of medications purchased abroad may be substandard. 27 However, because antibiotics reduce the duration and severity of traveler’s diarrhea and generally are well tolerated, 28 providing the traveler with the means for empiric self-treatment can effectively reduce morbidity from traveler’s diarrhea.

Waiting 24 hours to confirm the diagnosis of traveler’s diarrhea results in unnecessary discomfort and time away from activities. Therapy can be initiated after the first episode of “distressing” diarrhea (i.e., diarrhea that is uncomfortable or interferes with activities). 29 , 30 If symptoms resolve within 24 hours, no further treatment is necessary. 31 , 32 If diarrhea persists after one day, treatment should be continued for one or two more days. An algorithm for the treatment of traveler’s diarrhea is presented in Figure 1 . 33 , 34

Antibiotic selection is based on the likelihood that an invasive organism is present and on antibiotic resistance patterns. These factors are determined largely by travel destination. Although blood in the stool suggests invasive disease, fever is not a sensitive indicator of dysentery. Fluoroquinolones have been the drug of choice for traveler’s diarrhea in most parts of the world because of their efficacy against most enteropathogens. Rifaximin recently became available for the treatment of noninvasive diarrhea caused by E. coli . For persons traveling to destinations where noninvasive E. coli is the predominant pathogen (e.g., Mexico), rifaximin is a good choice. 35 , 36

In regions where invasive pathogens are responsible for a significant proportion of traveler’s diarrhea, quinolones should be used. Azithromycin (Zithromax) is recommended in places where quinoloneresistant Campylobacter is prevalent (e.g., Thailand). 15 , 16 Antibiotics used for the treatment of traveler’s diarrhea are listed in Table 4 . 16 , 32 , 37 Trimethoprim-sulfamethoxazole (Bactrim, Septra) and doxycycline are no longer recommended because of the development of widespread resistance. 12

Therapy that involves an antibiotic with loperamide (Imodium) often limits symptoms to one day. 38 , 39 Loperamide has antimotility and antisecretory effects and is taken as two 2–mg tablets after the first loose stool, followed by one tablet after each subsequent loose stool (maximum of 8 mg in 24 hours for two days). The use of loperamide in dysentery has been controversial because of concerns about prolonging illness, but it is now considered safe when combined with an antibiotic. 29 , 34 , 38 A conservative approach would be to use loperamide for dysentery only if combined with an antibiotic and if the traveler has a long trip or will have no toilet access.

Oral rehydration solutions generally are unnecessary in adults younger than 65 years. 40 However, all travelers with diarrhea should be encouraged to drink plenty of fluids and to replace lost electrolytes using foods such as salt crackers or broth.

Traveler’s Diarrhea in Infants, Children, and Pregnant Women

Traveler’s diarrhea is more common in young children than in adults, and they have a higher risk of dehydration and severe illness. 41 Parents should seek immediate medical attention if their child shows signs of moderate to severe dehydration, bloody diarrhea, a temperature higher than 39°C (102°F), or persistent vomiting. Few data exist on the treatment of diarrhea in children. The use of oral rehydration solutions is essential, and parents should include prepackaged packets (to be mixed with safe water) in their travel kits. These packets are available in camping stores in the United States or in pharmacies in other countries.

Because infants and toddlers normally can have three or more loose stools, an alternate definition of diarrhea in this age group is a twofold increase in the frequency of unformed stool. 37 Nursing infants should continue to breastfeed on demand, and infants and older children should be offered their usual food.

Fluoroquinolones are not approved by the U.S. Food and Drug Administration (FDA) for use in children, and rifaximin is approved only for children 12 years and older. Therefore, azithromycin is the drug of choice for most children with traveler’s diarrhea. 37 Another option is nalidixic acid (Neggram) in a dosage of 55 mg per kg per day divided into four doses, not to exceed 1 g in 24 hours. 37 Loperamide is approved for children older than two years, but should not be used in children with dysentery. Bismuth subsalicylate should be avoided for prophylaxis in children because of the possible risk of Reye’s syndrome.

Pregnant women may be at higher risk of traveler’s diarrhea than nonpregnant women because of lowered gastric acidity and increased gastrointestinal transit time. 42 Quinolones (FDA pregnancy category C) generally are not advised during pregnancy, but azithromycin (FDA pregnancy category B) is safe. Oral rehydration should be emphasized. Although rifaximin is not absorbed, the safety of this medication in pregnant women has not been established. Loperamide (FDA pregnancy category B) may be used, but bismuth subsalicylate (FDA pregnancy category D) should be avoided. Being careful with food and water is particularly important during pregnancy because infections such as listeriosis can cause miscarriage, and hepatitis E can result in maternal mortality.

Complications

Dehydration is the main complication of traveler’s diarrhea, especially in children and older adults. Because E. coli O157:H7 is a rare cause of traveler’s diarrhea, there is little risk of hemolyticuremic syndrome. Other complications include Guillain-Barré syndrome after Campylobacter enteritis, Reiter’s syndrome (especially in persons who are HLA-B27 positive), Clostridium difficile colitis after antibiotic use, and postinfectious irritable bowel. These conditions may appear after the traveler has returned home.

If diarrhea persists despite antibiotic treatment, medical attention should be sought. Parasitic causes should be suspected in travelers who return with prolonged diarrhea or who do not respond to antibiotics. For those traveling to remote areas for extended periods, it is reasonable to discuss empiric treatment of protozoal infections (e.g., metronidazole [Flagyl] 250 mg three times a day for five days or tinidazole [Fasigyn] in a single 2–g dose for Giardia). 43

Resources such as the Travelers’ Health section of the CDC Web site ( http://www.cdc.gov/travel/diarrhea.htm ) or commercial sites such as Travel Health Online ( http://www.tripprep.com ) can keep physicians up to date on the epidemiology and resistance patterns of traveler’s diarrhea. Better preventive and prophylactic strategies will be needed until newer antibiotics become available and the sanitation and hygiene in developing countries improve.

von Sonnenburg F, Tornieporth N, Waiyaki P, Lowe B, Peruski LF , DuPont HL, et al. Risk and aetiology of diarrhoea at various tourist destinations.. Lancet. 2000;356:133-4.

Castelli F, Pezzoli C, Tomasoni L. Epidemiology of travelers’ diarrhea.. J Travel Med. 2001;8(suppl 2):S26-S30.

Hill DR. Occurrence and self-treatment of diarrhea in a large cohort of Americans traveling to developing countries.. Am J Trop Med Hyg. 2000;62:585-9.

Steffen R, Sack RB. Epidemiology. In: Ericsson CD, DuPont HL, Steffen R, eds. Travelers’ diarrhea. Hamilton, Ont.: BC Decker, 2003:112–23.

Jiang ZD, Okhuysen PC, Guo DC, He R, King TM, DuPont HL, et al. Genetic susceptibility to enteroaggregative Escherichia coli diarrhea: polymorphism in the interleukin–8 promotor region.. J Infect Dis. 2003;188:506-11.

Hoge CW, Shlim DR, Echeverria P, Rajah R, Herrmann JE, Cross JH. Epidemiology of diarrhea among expatriate residents living in a highly endemic environment. JAMA. 1996;275:533-8.

Hardie RM, Wall PG, Gott P, Bardhan M, Bartlett LR. Infectious diarrhea in tourists staying in a resort hotel.. Emerg Infect Dis. 1999;5:168-71.

Daniels NA, Neimann J, Karpati A, Parashar UD, Greene KD, Wells JG, et al. Traveler’s diarrhea at sea: three outbreaks of waterborne enterotoxigenic Escherichia coli on cruise ships.. J Infect Dis. 2000;181:1491-5.

Ansdell VE, Ericsson CD. Prevention and empiric treatment of traveler’s diarrhea.. Med Clin North Am. 1999;83:945-73

Mensah P, Yeboah-Manu D, Owusu-Darko K, Ablordey A. Street foods in Accra, Ghana: how safe are they?. Bull World Health Organ. 2002;80:546-54.

Adachi JA, Mathewson JJ, Jiang ZD, Ericsson CD, DuPont HL. Enteric pathogens in Mexican sauces of popular restaurants in Guadalajara, Mexico, and Houston, Texas.. Ann Intern Med. 2002;136:884-7.

Jiang ZD, Lowe B, Verenkar MP, Ashley D, Steffen R, Tornieporth N, et al. Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay).. J Infect Dis. 2002;185:497-502.

Adachi JA, Jiang ZD, Mathewson JJ, Verenkar MP, Thompson S, Martinez-Sandoval F, et al. Enteroaggregative Escherichia coli as a major etiologic agent in traveler’s diarrhea in 3 regions of the world.. Clin Infect Dis. 2001;32:1706-9.

Taylor DN, Houston R, Shlim DR, Bhaibulaya M, Ungar BL, Echeverria P. Etiology of diarrhea among travelers and foreign residents in Nepal.. JAMA. 1988;260:1245-8.

Kuschner RA, Trofa AF, Thomas RJ, Hoge CW, Pitarangsi C, Amato S, 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;21:536-41.

Hoge CW, Gambel JM, Srijan A, Pitarangsi C, Echeverria P. Trends in antibiotic resistance among diarrheal pathogens isolated in Thailand over 15 years.. Clin Infect Dis. 1998;26:341-5.

Sanders JW, Isenbarger DW, Walz SE, Pang LW, Scott DA, Tamminga C, 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;67:533-8.

Tauxe RV, Swerdlow DL, Hughes JM. Foodborne disease. In: Mandell GL, Douglas RG, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone, 2000:1150–65.

Barbier HM, Diaz JH. Prevention and treatment of toxic seafoodborne diseases in travelers.. J Travel Med. 2003;10:29-37.

Kozicki M, Steffen R, Schar M. ‘Boil it, cook it, peel it or forget it’: does this rule prevent travellers’ diarrhoea?. Int J Epidemiol. 1985;14:169-72.

Mattila L, Siitonen A, Kyronseppa H, Simula II, Peltola H. Risk behavior for travelers’ diarrhea among Finnish travelers.. J Travel Med. 1995;2:77-84.

Backer H. Water disinfection for international and wilderness travelers.. Clin Infect Dis. 2002;34:355-64.

RendiWagner P, Kollaritsch H. Drug prophylaxis for travelers’ diarrhea.. Clin Infect Dis. 2002;34:628-33.

Steffen R, Heusser R, DuPont HL. Prevention of travelers’ diarrhea by nonantibiotic drugs.. Rev Infect Dis. 1986;8(suppl 2):S151-9.

Oksanen PJ, Salminen S, Saxelin M, Hamalainen P, Ihantola-Vormisto A, Muurasniemi-Isoviita L, et al. Prevention of travellers’ diarrhoea by Lactobacillus GG.. Ann Med. 1990;22:53-6.

Hilton E, Kolakowski P, Singer C, Smith M. Efficacy of Lactobacillus GG as a diarrheal preventive in travelers.. J Travel Med. 1997;4:41-3.

World Health Organization. Substandard and counterfeit medicines. Fact sheet no. 275, November 2003. Accessed online April 6, 2005, at: http://www.who.int/mediacentre/factsheets/2003/fs275 .

De Bruyn G, Hahn S, Borwick A. Antibiotic treatment for travellers’ diarrhoea.. Cochrane Database Syst Rev. 2005;;1:CD002242.

Shlim DR. Self diagnosis and treatment of traveler’s diarrhea. In: Keystone JS, Kozarsky PE, Freedman DO, Nothdurft HD, Connor BA, eds. Travel medicine. St. Louis: Mosby, 2003:201–4.

Ericsson CD. Travelers’ diarrhea: epidemiology, prevention, and self-treatment.. Infect Dis Clin North Am. 1998;12:285-303.

Salam I, Katelaris P, Leigh-Smith S, Farthing MJ. Randomised trial of singledose ciprofloxacin for travellers’ diarrhoea.. Lancet. 1994;344:1537-9.

Adachi JA, Ericsson CD, Jiang ZD, DuPont MW, Martinez-Sandoval F, Knirsch C, 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;37:1165-71.

DuPont HL, Mattila L. Antimicrobial treatment: an algorithmic approach. In: Ericsson CD, DuPont HL, Steffen R, eds. Travelers’ diarrhea. Hamilton, Ont.: BC Decker, 2003:227–37.

Adachi JA, OstroskyZeichner L, DuPont HL, Ericsson CD. Empirical antimicrobial therapy for traveler’s diarrhea.. Clin Infect Dis. 2000;31:1079-83.

DuPont HL, Jiang ZD, Ericsson CD, Adachi JA, Mathewson JJ, DuPont MW, et al. Rifaximin versus ciprofloxacin for the treatment of traveler’s diarrhea: a randomized, double-blind clinical trial.. Clin Infect Dis. 2001;33:1807-15.

Steffen R, Sack DA, Riopel L, Jiang ZD, Sturchler M, Ericsson CD, et al. Therapy of travelers’ diarrhea with rifaximin on various continents.. Am J Gastroenterol. 2003;98:1073-8.

Stauffer WM, Konop RJ, Kamat D. Traveling with infants and young children. Part III: travelers’ diarrhea.. J Travel Med. 2002;9:141-50.

Murphy GS, Bodhidatta L, Echeverria P, Tansuphaswadikul S, Hoge CW, Imlarp S, et al. Ciprofloxacin and loperamide in the treatment of bacillary dysentery.. Ann Intern Med. 1993;118:582-6.

Taylor DN, Sanchez JL, Candler W, Thornton S, McQueen C, Echeverria P. Treatment of travelers’ diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled randomized trial.. Ann Intern Med. 1991;114:731-4.

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;28:1286-9.

Pitzinger B, Steffen R, Tschopp A. Incidence and clinical features of traveler’s diarrhea in infants and children.. Pediatr Infect Dis J. 1991;10:719-23.

Samuel BU, Barry M. The pregnant traveler.. Infect Dis Clin North Am. 1998;12:325-54.

Drugs for parasitic infections. Med Lett Drugs Ther. 2004;46:1-12.

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Travelers’ diarrhea: Clinical practice guidelines for pharmacists

Introduction.

Travelers’ diarrhea (TD) is the most common travel-related illness, affecting up to 70% of travelers to certain destinations. 1 Its etiology is predominantly bacterial, representing approximately 80% to 90% of illnesses, 1 including diarrheagenic Escherichia coli, Salmonella, Shigella and Campylobacter species, but it can also be caused by parasites, such as Giardia and Cryptosporidium , and viruses, such as norovirus. 1 , 2 Opportunity costs, changes to trip itineraries and seeking medical care abroad are just some of the consequences that can result from a bout of TD. Emerging data have affected the recommendations for the prevention and treatment of TD, resulting in the publication of a set of guidelines for the condition in a 2017 supplement to the Journal of Travel Medicine . 3 As highly accessible experts in pharmacotherapy, pharmacists are well positioned to address travel-related concerns, particularly regarding TD, at both the prescription counter and over-the-counter (OTC) aisle. Pharmacists can draw from the guidelines to ensure patients are counselled on safe and appropriate antibiotic therapy during international travel and can direct patients to important nonprescription products supported by the guidelines and provide advice on their safe and effective use. This article summarizes the key recommendations from the 2017 guidelines of interest to practising community pharmacists. Readers requiring additional information are encouraged to consult the full guideline publication. 3

Development of the guidelines

The International Society of Travel Medicine (ISTM) used a panel of experts with relevant experience in the disease’s management to formulate the Guidelines for the Prevention and Treatment of Travelers’ Diarrhea: A Graded Expert Panel Report. Despite ISTM not having a designated process and resources to develop clinical practice guidelines, the panel members attempted to follow the Institute of Medicine guideline standards and Grades of Recommendations, Assessment, Development and Evaluation (GRADE) framework. 3 Each recommendation in the guideline underwent the same procedures: “Recommendation formulation [with a threshold of 80% agreement among panel members], grading the quality of evidence in terms of the confidence in the estimates of the efficacy and harms of the intervention and grading the strength of the recommendation based on the balance of harms and benefits and knowledge of the values and preferences of the travelers.” 3 Prior to publication, the manuscript was peer-reviewed by experts in infectious diseases and travel medicine who were not involved in the development of the guidelines. Readers seeking additional details on guideline development are referred to the Journal of Travel Medicine . 3

TD definitions

TD has previously been classified quantitatively, based on the number of loose bowel movements experienced in a day (e.g., mild = 1-2 stools/24 hours, moderate = 3-5 stools/24 hours and severe = 6-9 stools/24 hours). 4 , 5 Classification is now qualitative, based on the functional impact TD has on the patient and his or her ability to participate in activities planned during travel ( Table 1 ).

Classifications of travelers’ diarrhea

Patients should be counselled on these definitions in order to properly recognize when to begin self-treatment and which treatments should be used (discussed below). It is important to emphasize the “functional impact” when educating, so that travelers can recognize the form of illness they are experiencing. For example, 1 episode with severe fever, cramping and bloody stools may be more impairing than 4 unformed stools without any other symptoms. Furthermore, as severe dysentery TD is typically accompanied by a fever, and traveling patients will likely not be carrying a thermometer, pharmacists should discuss its symptomatology so that patients can recognize this severe form of illness. Pharmacists should advise patients to seek medical assessment for TD lasting longer than 14 days, as persistent diarrhea may be associated with a higher frequency of certain bacteria, protozoal pathogens or other noninfectious conditions that may require targeted diagnosis and treatment.

TD prophylaxis

Antimicrobial resistance is a serious global health issue, necessitating the judicious use of antibiotics. For most travelers, antibiotics should not routinely be used for TD prophylaxis. However, antimicrobial prophylaxis can be considered for patients at a high risk for complications secondary to TD, such as those who have a clinically significant history of potential additional morbidity following an enteric infection (e.g., inflammatory bowel disease, reactive arthritis) or a chronic illness that predisposes them to TD (e.g., achlorhydria, gastrectomy) or its complications (e.g., immunocompromised, diabetes, renal dysfunction). 3 Other individuals who may be considered for TD prophylaxis include travelers who cannot afford to become sick with TD due to occupation or itinerary reasons (e.g., athlete in competition, musician, politician). 3 Because of the rapid efficacy of TD self-treatment and increasing rates of antimicrobial resistance, individual risk-benefit assessments and appropriate counselling must be performed before considering prophylaxis.

TD prophylaxis can be employed without antibiotics through the use of bismuth subsalicylate. Doses of 2.1 g/day or 4.2 g/day in 4 divided doses (with meals and bedtime) in either the liquid or tablet form have been studied and demonstrated a consistent protective effect against TD, upwards of 60%. 6 - 8 Despite robust evidence, its adverse effects, most commonly including black tongue and stools and least commonly being tinnitus, can be undesirable for traveling patients. 6 In addition, its contraindications in pediatric, pregnant, aspirin-allergic and aspirin-taking patients limit its use in the prevention of TD, and its frequent dosing may also affect adherence.

If antibiotic prophylaxis is warranted in a traveling patient, rifaximin is advised, 3 based on strong evidence of effectiveness, minimal antimicrobial resistance (excluding Campylobacter spp.) and favourable safety profile, as it is not systemically absorbed. Because of its resistance to Campylobacter spp., its effectiveness may not be as assured in South and Southeast Asia, where Campylobacter infection is more common. While 600 mg orally once daily is the standard prophylaxis dose for rifaximin, readers should be aware that it is currently available only in Canada as 550 mg tablets. The Committee to Advise on Tropical Medicine and Travel guidelines do not consider this difference in dose to be clinically significant 9 and therefore recommend that a regimen of 550 mg once daily can be used by Canadian travelers. The trials supporting rifaximin’s strong prophylactic protection against TD used a range of dosing regimens, from 200 mg to 1100 mg divided 1 to 3 times daily. 10 - 14 However, because of the risk of missing doses and the observed rebound infection following discontinuation of the drug, some clinicians advocate for a twice-daily regimen (200 mg or 550 mg) based on expert opinion. It should also be noted that effectiveness and safety have not been demonstrated beyond 2 weeks in multiple trials and thus may represent the best solution for short-term protection when needed. 15

Although they have long been prescribed for prophylaxis, fluoroquinolones are no longer recommended for prophylaxis of TD because of the emerging resistance of enteric pathogens. The use of fluoroquinolones exposes patients to potential harm to the peripheral and central nervous system, tendons, muscles and joints, as well as the possibility of Clostridium difficile –associated diarrhea. Therefore, based on its high-risk and low-benefit profile, the guidelines do not recommend the use of fluoroquinolones in TD prophylaxis. In addition, recommendations regarding azithromycin’s prophylactic use have not been determined in the 2017 guidelines. 3

Pharmacists are reminded to encourage patients to also practise food and water precautions to minimize their risk of exposure to TD-causing organisms. Frequent handwashing, especially prior to meals, with warm soap and water or the use of an alcohol-based hand sanitizer with ≥60% alcohol is recommended. 16 It is safest to eat food that is fully cooked and served hot, as raw or undercooked meals containing meat and fish are likely to be contaminated. 16 When selecting foods to eat abroad where hygiene and sanitation are inadequate or unknown, travelers should also be advised to avoid unpasteurized fruit juices, milks or cheeses, produce washed in local water sources and raw fruits that are unpeeled (e.g., strawberries), as opposed to fruits that are peeled by the traveler (e.g., bananas and mangoes). 16 Commercially bottled water with a preserved seal should be recommended for drinking, preparing food and beverages, making ice and brushing teeth. 16

Therapy for mild TD

Most cases of TD can be classified as mild: otherwise tolerable, nondistressing and does not interfere with planned activities. Because of increasing antimicrobial resistance and concerns regarding multidrug-resistant organisms, antibiotic conservation is advised. Therefore, antibiotic treatment is not recommended in patients with mild TD. Instead, supportive measures such as oral rehydration therapy and nonantibiotic, antimotility drugs such as loperamide can be used. Loperamide’s use in mild TD has been shown to decrease the duration of diarrhea and the frequency of passing unformed stools. 17 - 19 Although previously discouraged for TD treatment because of its antimotility effects and concerns about potential retention of pathogens in the gut, a number of observational studies support the safe and effective use of loperamide in the treatment of mild TD. 20 , 21

Loperamide and bismuth subsalicylate are the 2 OTC products with the most supportive evidence, with stronger evidence favoring loperamide over bismuth subsalicylate. 17 Other agents, such as activated charcoal or dimenhydrinate, are not recommended. Although loperamide is the recommended first-line agent, patients should be informed that if the diarrhea worsens or is accompanied by moderate-severe or invasive symptoms (1 or more of fever, moderate to severe abdominal pain or bloody diarrhea), then antibiotics should be used ( Table 2 ). To ensure ready access to antibiotic treatment if required while traveling, prescriptions should be dispensed to most travelers in advance of their departure. Filling medications at a Canadian pharmacy also prevents the exhaustion of the destination country’s medication supply and prevents the possible ingestion of international substandard or falsified medications. 22

Summary of treatment recommendations based on Canadian product availability

po, orally.

Therapy for moderate TD

TD can affect both a traveler’s well-being and finances, as illness may require the rebooking of flights, cancellation of major excursions and missing activities on the traveler’s itinerary. Patients with moderate illness may be treated with antibiotics, with or without adjunctive loperamide. Timely and effective self-treatment with antibiotics in moderate TD reduces the duration of illness to approximately 36 hours, with further reduction to less than 12 hours from combination therapy with loperamide. 9 , 23 - 25 Potential risks from antibiotic therapy, including the potential for acquisition of extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-PE) and C. difficile infection, must be weighed for each individual traveler against the benefits: (1) potentially favourable safety profiles from single-dose regimens and (2) theoretical mitigation of risk of developing long-term TD sequelae such as postinfectious irritable bowel syndrome. 20 , 26 - 30 However, more studies evaluating the nature and impact of these theoretical risks and benefits are needed.

Several class- and regimen-specific factors should be considered when choosing an antibiotic. Despite observational data of globally increasing resistance rates, 31 fluoroquinolones may still be used in the treatment of moderate TD. However, their use should be avoided in Southeast and South Asia, as widespread resistance, particularly against Campylobacter spp., has resulted in documented clinical failure. 32 These resistance rates and safety concerns regarding their potential for intestinal microbiota imbalance and musculoskeletal consequences have resulted in a nonunanimous recommendation by the guideline’s expert panel. Canadian readers should note that while ofloxacin is a fluoroquinolone listed for TD treatment in the guidelines, it is not currently marketed in an oral formulation in Canada. As an alternative to fluoroquinolones, azithromycin may also be considered for moderate TD, as studies indicate there is no significant difference in efficacy between azithromycin and fluoroquinolones. 9 However, it should be noted that as the TD classification changes from moderate to severe, the 2017 guidelines prefer azithromycin as the primary treatment option (discussed below). 3 Apart from concerns in Nepal, azithromycin has limited global resistance, and despite requiring increased concentrations to inhibit enterotoxigenic and enteroaggregative E. coli (ETEC and EAEC, respectively), this has not yet resulted in documented clinical failure. It also has a much more tolerable safety profile compared with fluoroquinolones, with the exception of nausea and vomiting, particularly when the single dose of 1000 mg is ingested. However, both azithromycin and fluoroquinolones potentially expose certain patients to the risk of QT prolongation and must be carefully considered for patients at risk of this, including those with a QTc interval >500 ms, advanced age, female sex and concomitant QTc-prolonging medications, such as some antidepressants and antipsychotics. 33

Finally, the guidelines also recommend rifaximin as another alternative for moderate TD. However, as the only rifaximin products currently licensed in Canada are 550 mg tablets, and the splitting of tablets is not recommended by the manufacturer, 34 product availability prevents Canadian patients from accessing the recommended treatment dose of 200 mg 3 times daily unless they purchase it abroad. As a poorly absorbed antibiotic, it has an excellent safety profile and limited global resistance rates; however, its use is cautioned for travel to regions with a high risk of invasive pathogens, such as Campylobacter, Shigella and Salmonella , because of its poor clinical success against these species. 35 , 36 A recent trial evaluating single high-dose rifaximin (1650 mg) in combination with loperamide was found to be comparable to single-dose levofloxacin (500 mg) and azithromycin (500 mg), with clinical cures of about 14 hours. 37

As mentioned previously, loperamide may be used either in combination therapy with antibiotics or as monotherapy for moderate TD. Its quick onset when used with antibiotics provides symptomatic relief in addition to curative treatment. Concerns about adverse effects, including disruption of the diversity of intestinal flora and ESBL-PE colonization, surrounding combination therapy remain unsubstantiated. Despite the apprehension of increasing a TD patient’s exposure to pathogens when motility is slowed, loperamide’s studied effectiveness has led to its safe recommendation as a solo therapy in nonsevere TD. 3 Other than constipation, which may occur from patients taking doses at too frequent intervals (patients should be advised that it has an onset of action of up to 1-2 hours), it is a well-tolerated agent. Combination therapy with loperamide has consistently demonstrated an advantage in time to clinical cure compared with antibiotics alone.

BOX 1 Key points regarding travelers’ diarrhea for pharmacists

The release of the 2017 guidelines for the prevention and treatment of travelers’ diarrhea has resulted in significant changes in the management of travelers’ diarrhea, many of which affect community pharmacy practice. The key points of interest to pharmacists are summarized here:

• •  Classification of TD
•  ○ TD severity should be based on a patient’s self-determination:
•   □  Mild : Tolerable, nondistressing and does not interfere with planned activities
•   □  Moderate : Distressing or interfering with planned activities
•   □  Severe : Incapacitating or completing stopping all planned activities, including dysentery and nondysentery presentations
•   □  Persistent : Diarrhea lasting ≥2 weeks
• •  TD prophylaxis
•  ○ Prophylaxis is not routinely used but can be considered for patients at high risk of health-related complications secondary to TD such as:
•   □ prior clinically significant history of potential additional morbidity following an enteric infection (e.g., inflammatory bowel disease, reactive arthritis) and
•   □ chronic illness that predisposes patient to TD (e.g., achlorhydria, gastrectomy) or its complications (e.g., immunocompromised, diabetes, renal dysfunction).
•  ○ Prophylaxis may be considered for travelers who cannot afford to become sick with TD because of their occupation or itinerary reasons (e.g., athlete in competition, musician, politician).
•   □ Bismuth subsalicylate may be considered for most travelers as prophylaxis.
•   □ If antibiotic prophylaxis is indicated, rifaximin is the recommended agent.
• •  Mild TD
•  ○ Patients can use loperamide for the treatment of mild TD to decrease the duration of diarrhea and frequency of passing unformed stool.
• •  Moderate TD
•  ○ Functional impairment and itinerary changes are the main factors to consider when using self-determining to use antibiotics for moderate TD.
•   □ Antibiotic treatment options available in Canada are azithromycin and fluoroquinolones (when traveling outside of Southeast Asia).
•   □ Because of emerging global resistance and efficacy, pharmacists may notice a shift in prescribing practices, in which azithromycin is used as the first-line treatment for both moderate and severe TD.
•  ○ Loperamide can be used either alone or as an adjunct to antibiotics.
• •  Severe TD
•  ○ Travelers should be educated on how to self-diagnose dysentery (presence of blood in the stool, possibly accompanied by fever and/or abdominal pain) to determine appropriate treatment measures.
•  ○ Antibiotics should be used for severe travelers’ diarrhea, both dysentery and nondysentery, with azithromycin being the antibiotic of choice.
•   □ Loperamide may also be used as an adjunct to azithromycin, in the absence of dysentery.

Therapy for severe TD

Severe TD includes both nondysenteric watery diarrhea affecting a traveler’s quality of life and dysentery. Both presentations are important to consider and discern as this guides the antibiotic management options. The main distinction between the 2 types of severe diarrhea is the presence of blood in the stool (possibly accompanied by fever and/or abdominal pain), as this depicts the hallmark clinical presentation of dysentery.

BOX 2 Resources for additional information regarding travelers’ diarrhea and other travel-related concerns

• • International Society of Travel Medicine ( www.istm.org/ )
•  ○ ISTM offers a Certificate in Travel Health (CTH) to health care practitioners who have developed competency in providing travel medicine services. Pharmacists interested in expanding their knowledge and providing more comprehensive travel medicine services are encouraged to write the CTH examination.
• • Committee to Advise on Tropical Medicine and Travel ( www.canada.ca/en/public-health/services/travel-health/about-catmat.html )
• • Centre for Disease Control and Prevention Health Information for International Travel, otherwise known as the CDC Yellow Book ( wwwnc.cdc.gov/travel/page/yellowbook-home )
• • Travel Health Pro ( travelhealthpro.org.uk/ )
• • American College of Gastroenterology (ACG) Clinical Guideline: Diagnosis, Treatment and Prevention of Acute Diarrheal Infections in Adults 4
•  ○ Readers should note that information presented in this guideline related to definitions of TD and management options based on the number of loose stools has been redefined in more recent guidelines; however, the document still provides valuable guidance on symptom management.
• • Pharmacy5in5 TD Infographic ( https://uwaterloo.ca/pharmacy/sites/ca.pharmacy/files/uploads/files/tdinfographic.pdf )
•  ○ Pharmacy5in5 is a free online learning platform designed by pharmacists for pharmacists and pharmacy technicians. Pharmacists interested in testing their TD knowledge are encouraged to complete the module on TD.

For both nondysenteric and dysenteric TD, azithromycin is the preferred agent because of its low global resistance against invasive pathogens and tolerable safety profile. 38 - 41 A single-dose antibiotic regimen can be tried initially and continued daily for up to 3 days if symptoms are not resolved within 24 hours. Therefore, pharmacists should ensure patients are provided sufficient antibiotics to allow for both a single dose and a complete 3-day regimen. Fluoroquinolones may be used to treat severe, nondysenteric TD, provided the traveler is not going to Southeast or South Asia (due to Campylobacter resistance) and a proper risk-benefit assessment has been completed regarding its safety profile. Rifaximin may also be used to treat severe, nondysenteric TD, provided the traveler is not going to a region that has a high risk of invasive pathogens, due to the drug’s lack of efficacy against them. However, as mentioned, this product is not available in a suitable strength in Canada and would need to be acquired by patients abroad, limiting its applicability to Canadian travelers. As with moderate diarrhea, combination therapy consisting of antibiotics with loperamide improves time to clinical cure compared with antibiotics alone. However, the combination should not be employed when dysentery is present.

Additional consensus statements of interest to pharmacists

Despite their appeal, prebiotics and probiotics are not currently recommended to prevent or treat TD. More research is needed to determine their use in TD, as questions remain regarding formulation, dosing, strain or combination for the right condition or individual, knowledge of the host microbiome and mechanisms of action. 3 In addition, there is an emerging concern involving the association between travel, the use of antibiotics in TD and the colonization of multidrug-resistant organisms. Carriage is mostly transient but can be persistent 1 year posttravel in approximately 10% of travelers and transmitted to household contacts. 3 Pharmacists should discuss with patients this multidimensional risk regarding travel, TD and the use of antibiotics abroad. Female patients presenting with a urinary tract infection with recent travel should have a urine culture to ensure appropriate antibiotic choice.

Changes to the definitions of illness severity to be largely based on its functional impact on patients (and treatment recommendations based on these symptoms) make it increasingly important for pharmacists to have shared decision-making discussions with patients, considering their individual risk of TD or its complications, their itinerary and goals of their travel and their ability to cope with symptoms abroad. As patients will often need to make symptom assessment and treatment decisions without pharmacist assistance abroad, these discussions at the time of dispensing are especially important to ensure optimal outcomes. ■

Key points for pharmacists related to the prevention and treatment of TD are summarized in Box 1 and the provided infographic, with additional resources that may be of interest provided in Box 2.

Author Contributions: H. Fernandes initiated the article and wrote and reviewed the final draft. S. Houle, A. Johal and M. Riddle wrote and reviewed the final draft.

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding: The authors received no financial support for the research, authorship and/or publication of this article.

• Patient Care & Health Information
• Diseases & Conditions
• Traveler's diarrhea

Traveler's diarrhea may get better without any treatment. But while you're waiting, it's important to try to stay hydrated with safe liquids, such as bottled water or water with electrolytes such as an oral rehydration solution (see below). If you don't seem to be improving quickly, several medicines are available to help relieve symptoms.

Anti-motility agents. These medicines — which include loperamide and drugs containing diphenoxylate — provide prompt but temporary relief by:

• Reducing muscle spasms in your gastrointestinal tract.
• Slowing the transit time through your digestive system.
• Allowing more time for absorption.

Anti-motility medicines aren't recommended for infants or people with a fever or bloody diarrhea. This is because they can delay clearance of the infectious organisms and make the illness worse.

Also, stop using anti-motility agents after 48 hours if you have stomach pain or if your symptoms worsen and your diarrhea continues. In such cases, see a doctor. You may need blood or stool tests and treatment with an antibiotic.

• Bismuth subsalicylate. This nonprescription medicine can decrease the frequency of your stools and shorten the length of your illness. However, it isn't recommended for children, pregnant women or people who are allergic to aspirin.
• Antibiotics. If you have more than four loose stools a day or severe symptoms, including a fever or blood, pus or mucus in your stools, a doctor may prescribe a course of antibiotics.

Before you leave for your trip, talk to your doctor about taking a prescription with you in case you get a serious bout of traveler's diarrhea.

Avoiding dehydration

Dehydration is the most likely complication of traveler's diarrhea, so it's important to try to stay well hydrated.

An oral rehydration salts (ORS) solution is the best way to replace lost fluids. These solutions contain water and salts in specific proportions to replenish both fluids and electrolytes. They also contain glucose to enhance absorption in the intestinal tract.

Bottled oral rehydration products are available in drugstores in developed areas, and many pharmacies carry their own brands. You can find packets of powdered oral rehydration salts, labeled World Health Organization (WHO)- ORS , at stores, pharmacies and health agencies in most countries. Reconstitute the powder in bottled or boiled water according to the directions on the package.

If these products are unavailable, you can prepare your own rehydrating solution in an emergency by mixing together:

• 3/4 teaspoon table salt.
• 2 tablespoons sugar.
• 1 quart uncontaminated bottled or boiled water.
• Sugar-free flavor powder, such as Crystal Light (optional).

You or your child can drink the solution in small amounts throughout the day as a supplement to solid foods or formula, as long as dehydration persists. Small amounts reduce the likelihood of vomiting. Breastfed infants also can drink the solution but should continue nursing on demand.

If dehydration symptoms — such as dry mouth, intense thirst, little or no urination, dizziness, or extreme weakness — don't improve, seek medical care right away. Oral rehydration solutions are intended only for urgent short-term use.

Lifestyle and home remedies

If you do get traveler's diarrhea, avoid caffeine, alcohol and dairy products, which may worsen symptoms or increase fluid loss. But keep drinking fluids.

Drink canned fruit juices, weak tea, clear soup, decaffeinated soda or sports drinks to replace lost fluids and minerals. Later, as your diarrhea improves, try a diet of easy-to-eat complex carbohydrates, such as salted crackers, bland cereals, bananas, applesauce, dry toast or bread, rice, potatoes, and plain noodles.

You may return to your normal diet as you feel you can tolerate it. Add dairy products, caffeinated beverages and high-fiber foods cautiously.

Preparing for your appointment

Call a doctor if you have diarrhea that is severe, lasts more than a few days or is bloody. If you are traveling, call an embassy or consulate for help locating a doctor. Other signs that you should seek medical attention include:

• A fever of 102 F (39 C) or higher.
• Ongoing vomiting.
• Signs of severe dehydration, including a dry mouth, muscle cramps, decreased urine output, dizziness or fatigue.

If you have diarrhea and you've just returned home from a trip abroad, share that trip information with your doctor when you call to make an appointment.

Here's some information to help you get ready, and what to expect.

Information to gather in advance

• Pre-appointment instructions. At the time you make your appointment, ask whether there are immediate self-care steps you can take to help recover more quickly.
• Symptom history. Write down any symptoms you've been experiencing and for how long.
• Medical history. Make a list of your key medical information, including other conditions for which you're being treated and any medicines, vitamins or supplements you're currently taking.
• Questions to ask your health care professional. Write down your questions in advance so that you can make the most of your time.

The list below suggests questions to ask about traveler's diarrhea.

• What's causing my symptoms?
• Are there any other possible causes for my symptoms?
• What kinds of tests do I need?
• What treatment approach do you recommend?
• Are there any possible side effects from the medicines I'll be taking?
• Will my diarrhea or its treatment affect the other health conditions I have? How can I best manage these conditions together?
• What is the safest way for me to rehydrate?
• Do I need to follow any dietary restrictions and for how long?
• How soon after I begin treatment will I start to feel better?
• How long do you expect a full recovery to take?
• Am I contagious? How can I reduce my risk of passing my illness to others?
• What can I do to reduce my risk of this condition in the future?

In addition to the questions that you've prepared, don't hesitate to ask questions as they occur to you during your appointment.

What to expect from your doctor

Your doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over points you want to talk about in-depth. Your doctor may ask:

• What are your symptoms?
• When did you first begin experiencing symptoms?
• Have you traveled recently?
• Where did you travel?
• Have you taken any antibiotics recently?
• Have your symptoms been getting better or worse?
• Have you noticed any blood in your stools?
• Have you experienced symptoms of dehydration, such as muscle cramps or fatigue?
• What treatments have you tried so far, if any?
• Have you been able to keep down any food or liquid?
• Are you pregnant?
• Are you being treated for any other medical conditions?
• Feldman M, et al., eds. Infectious enteritis and proctocolitis. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 11th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed May 25, 2021.
• LaRocque R, et al. Travelers' diarrhea: Microbiology, epidemiology, and prevention. https://www.uptodate.com/contents/search. Accessed May 26, 2021.
• Ferri FF. Traveler diarrhea. In: Ferri's Clinical Advisor 2023. Elsevier; 2023. https://www.clinicalkey.com. Accessed April 28, 2023.
• Diarrhea. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/digestive-diseases/diarrhea. Accessed April 27, 2023.
• Travelers' diarrhea. Centers for Disease Control and Prevention. https://wwwnc.cdc.gov/travel/yellowbook/2020/preparing-international-travelers/travelers-diarrhea. Accessed April 28, 2023.
• LaRocque R, et al. Travelers' diarrhea: Clinical manifestations, diagnosis, and treatment. https://www.uptodate.com/contents/search. Accessed May 26, 2021.
• Khanna S (expert opinion). Mayo Clinic. May 29, 2021.

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INTRODUCTION

The treatment and prevention of travelers' diarrhea are discussed here. The epidemiology, microbiology, clinical manifestations, and diagnosis of travelers' diarrhea are discussed separately. (See "Travelers' diarrhea: Epidemiology, microbiology, clinical manifestations, and diagnosis" .)

Clinical approach  —  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. Antimotility agents can provide symptomatic relief but should not be used when bloody diarrhea is present. Antimicrobial therapy shortens the disease duration, but 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. 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 [ 11,12 ]. 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.

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Diarrhoea - prevention and advice for travellers: Scenario: Diarrhoea - prevention and advice for travellers

Last revised in September 2023

Covers the prevention of travellers' diarrhoea, and advice for people who are at risk of travellers' diarrhoea.

Scenario: Diarrhoea - prevention and advice for travellers

From age 1 month onwards.

How should I assess the risk of acquiring travellers' diarrhoea before travelling?

• Low-risk areas (fewer than 7% of travellers experience travellers' diarrhoea) include Western Europe, the USA, Canada, Japan, Australia, and New Zealand. 
• Intermediate risk areas (8–20% of travellers experience travellers' diarrhoea) include southern Europe, Israel, South Africa, and some Caribbean and Pacific islands.
• High-risk areas (more than 20% of travellers experience travellers' diarrhoea) include Africa, Latin America, the Middle East, and most parts of Asia. 
• For up-to-date risk assessment of individual countries and the requirement for strict food, water, and personal hygiene precautions , see the National Travel Health Network and Centre (NaTHNaC) website ( www.nathnac.org ). 
• Local amenities and sanitation — in areas with low standards of hygiene and sanitation and poor control over the safety of food, drink, and drinking water, the risk of acquiring travellers' diarrhoea is high. 
• How the person will be travelling — backpackers, campers, adventurers, and passengers on cruise ships are at increased risk.
• When the person will be travelling — the peak incidence of travellers' diarrhoea is in the warmer months. Lower rates occur in winter.
• What the person eats — for example, risks are associated with food from buffets, restaurants, and street vendors, and certain types of food such as raw fish and seafood, salads, and meat and poultry that have been inadequately cooked. For more information, see Advice on food and drink . 
• Review the person's susceptibility to traveller's diarrhoea and their risk of complications.  For more information on which groups of people are considered to be at higher risk, see the section on  Risk factors . 
• Enquire about access to medical amenities  — this is particularly important for those travelling to remote areas with few or no medical amenities (especially trekking and camping).
• Discuss whether visits to high-risk areas are essential (particularly if the person is at increased risk of complications) and whether they are suitably prepared (for example, if backpacking through remote areas).

Basis for recommendation

The recommendations about how to assess a person's risk of acquiring travellers' diarrhoea are largely based on expert opinion in a World Health Organisation (WHO) publication International Travel and Health [ WHO, 2012 ], the BMJ Best Practice guideline Traveller's Diarrhoea [ BMJ Best Practice, 2021 ], the Centres for Disease Control (CDC) guidance   Travelers' diarrhea -  Preparing International Travelers [ CDC, 2023a ], and the guidance on Travellers' diarrhoea from the National Travel Health Network and Centre (NaTHNaC) [ NaTHNaC, 2023 ].

How should I manage someone at low or intermediate risk of travellers' diarrhoea?

• Advise the person that most travellers' diarrhoea is caused by the consumption of contaminated food or water.
• Reassure the person that no special precautions (other than basic hygiene measures) are required when travelling to locations with a high standard of hygiene.
• Provide information on  food hygiene and safe drinking water if the person is travelling to locations with lower standards of hygiene and sanitation.
• Offer advice regarding  self-management  and when to seek medical advice if the person develops diarrhoea during their trip.

The recommendations on managing people at low or intermediate risk of travellers' diarrhoea are largely based on expert opinion regarding general advice to offer travellers in a World Health Organisation (WHO) publication International Travel and Health [ WHO, 2012 ], the American College of Gastroenterologists guideline Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults [ Riddle et al, 2016 ], the BMJ Best Practice guideline Traveller's Diarrhoea [ BMJ Best Practice, 2021 ], the Centres for Disease Control (CDC) guidance Travelers' diarrhea -  Preparing International Travelers [ CDC, 2023a ] and the guidance on Travellers' diarrhoea from the National Travel Health Network and Centre (NaTHNaC) [ NaTHNaC, 2023 ]. 

How should I manage someone at high risk of travellers' diarrhoea?

• For further information, see  advice on food and drink .
• Warn travellers about the risk of food- and water-borne infections and how to avoid potentially contaminated recreational water. Contaminated recreational water can be found in inadequately treated pools, water playgrounds, hot tubs, spas, and freshwater or seawater. Potential illness-causing contaminants include human faeces, animal waste, sewage, or wastewater runoff.
• Antibiotic prophylaxis may be appropriate for certain high-risk travellers. For more information, see the section on  prophylactic antibiotics .
• The use of bismuth subsalicylate and probiotics for prophylaxis is not recommended.
• Antidiarrhoeal drugs (such as loperamide) should not be taken prophylactically.
• Consider whether 'stand by' antibiotic treatment (to use if affected) is appropriate. For more information, see the section on  'stand-by' antibiotics .
• Inform the person that there are no universal vaccines to cover all the infections which may cause travellers' diarrhoea.  However, travellers to risky areas must seek advice about appropriate vaccination against other infections that cause gastrointestinal effects, such as cholera, hepatitis A, and typhoid. For further information on vaccines recommended for overseas travel, extended holidays, or working overseas, see the CKS topic on Immunizations - travel .
• For further information, see  advice on managing travellers' diarrhoea .

The recommendations on managing people at high risk of travellers' diarrhoea are largely based on expert opinion in a World Health Organisation (WHO) publication International Travel and Health [ WHO, 2012 ], the American College of Gastroenterologists guideline Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults [ Riddle et al, 2016 ], the BMJ Best Practice guideline Traveller's Diarrhoea [ BMJ Best Practice, 2021 ], the Centres for Disease Control (CDC) guidelines Travelers' diarrhea -  Preparing International Travelers [ CDC, 2023a ] and Food and water precautions - Preparing International Travelers [ CDC, 2023c ] and the guidance on Travellers' diarrhoea from the National Travel Health Network and Centre (NaTHNaC) [ NaTHNaC, 2023 ].

What food and drink measures are recommended for preventing travellers' diarrhoea?

• Hands should always be washed with soap and water before handling and consuming food (particularly after contact with raw meat and uncooked food), using the toilet, or caring for an ill person.
• If soap and water are not available, an alcohol-based hand sanitiser can be used as an alternative until it is possible to wash the hands. Note that hand sanitiser is not effective when hands are greasy or visibly dirty and has limited effectiveness against Cryptosporidium and norovirus.
• Raw fish and seafood should be avoided, as well as shellfish, and any meat or poultry that has not been thoroughly cooked.
• Risks are associated with food from buffets, restaurants, and street vendors. Food from these sources should be avoided, if it has neither been kept hot, nor refrigerated or kept on ice.
• Cooked food that has been in contact with raw food, or contains raw or uncooked eggs (such as homemade mayonnaise), should be avoided.
• If hygiene and sanitation are likely to be inadequate, avoid salads, uncooked vegetables, and unpasteurised fruit juices. Fruits and vegetables that can be peeled by the end-user are suitable choices (fruits and vegetables with damaged skins should be avoided).
• Ice should be avoided, unless it has been made from safe water.
• Unpasteurised (raw) milk or cheese should be avoided.
• Commercially prepared carbonated drinks, pasteurised drinks, fruit juices, and alcoholic beverages are usually safe provided they are in factory-sealed containers. The surface of the container should be wiped clean and dried if the drink is to be consumed directly from the container.
• Tap water should be avoided for drinking, preparing food, making ice, cooking, and brushing teeth, unless there is reasonable certainty it is safe.
• Bottled water is the safer choice for drinking water. The seal must not have been tampered with.
• Water should be boiled (for at least 1 minute) if its safety for drinking is in doubt.
• Other options include micropore filtering and the use of disinfectant preparations. These might be more relevant for people travelling to areas where there is little or no access to safe drinking water.
• A fact sheet on Food and Water Hygiene is available on the Travel Health Pro website ( travelhealthpro.org.uk ).

The recommendations on food and drink precautions to reduce the risk of travellers' diarrhoea are based on expert opinion in the Centres for Disease Control (CDC) guidance on Travelers' diarrhea -  Preparing International Travele rs [ CDC, 2023a ] and Travelers' diarrhea -  Food & Water precautions [ CDC, 2023c ] and the guidance on Travellers' diarrhoea from the National Travel Health Network and Centre (NaTHNaC) [ NaTHNaC, 2023 ].

The CDC states that [ CDC, 2023a ]:

• Poor hygiene practices in local restaurants and underlying hygiene and sanitation infrastructure deficiencies are likely the largest contributors to the risk for travellers' diarrhoea.
• While measures such as avoiding certain food and food establishment types and ensuring food is thoroughly cooked, can help to reduce the risk of travellers' diarrhoea, it is acknowledged that some of these measures may be difficult to follow while travelling, and that some food safety factors are out of the traveller's control. Risk can therefore never be fully eliminated.

What should I advise about self-management of travellers' diarrhoea?

• That most episodes of travellers' diarrhoea are short-lived and self-limiting, and last a few days. 
• To consider purchasing sachets of oral rehydration salts before travelling as they may not be available at the destination. 
• For infants, breastfeeding should not be interrupted.
• Hydration must be maintained, for example with boiled, treated, or sealed bottled water. Most otherwise healthy adults can stay hydrated by eating and drinking as normal.
• Alcohol and other drinks and beverages with a diuretic effect (such as coffee and tea) and overly sweet drinks (in large quantities) should be avoided.
• For more severe symptoms, or people prone to complications from dehydration, oral rehydration powders diluted into clean drinking water can help to correct electrolyte imbalances.
• Immediate medical attention is required if children show signs of dehydration such as restlessness or irritability, great thirst, sunken eyes, and dry skin with reduced elasticity.
• Loperamide is usually considered the standard treatment when rapid control of symptoms is required — for example during travelling where toilet amenities are limited or unavailable. 
• Bismuth subsalicylate is more suitable for mild diarrhoea; loperamide has a faster onset of action and is more effective than bismuth subsalicylate   for controlling diarrhoea and cramping.
• Bismuth subsalicylate is not suitable for people with aspirin allergy, renal insufficiency, gout, severe enteric disease or HIV (risk of bismuth absorption), or people who are taking an anticoagulant such as warfarin, or pregnant or breastfeeding women. Darkened tongue and stools are common adverse effects.
• Advise the person  not  to use loperamide or bismuth subsalicylate (for example Pepto-Bismol ® ) if they have blood or mucous in the stool and/or high fever or severe abdominal pain. 
• Loperamide should not be used in children younger than 12 years of age because of concerns that it may cause intestinal obstruction. 
• Bismuth subsalicylate must not be used in children younger than 16 years of age because of the possible association between salicylates and Reye's syndrome. 
• Stools are blood-stained, profuse and watery, or there is high or persistent fever or severe abdominal pain.
• Severe diarrhoea occurs in infants or elderly people, or a child is unwell with travellers' diarrhoea and symptomatic treatment is needed.
• The person becomes dehydrated — particularly in infants and children (restlessness or irritability, very thirsty, sunken eyes, and dry skin with reduced elasticity); or it is difficult to maintain adequate hydration.
• Diarrhoea does not begin to improve within 24–36 hours despite self-treatment. 
• There is a medical comorbidity (for example immunosuppression or gastrointestinal disorder).
• NHS:  www.nhs.uk — Access to healthcare abroad .
• The National Travel Health Network and Centre (NaTHNaC):  www.nathnac.net .
• The 'Fit for travel' website provided by NHS Scotland:  www.fitfortravel.scot.nhs.uk .
• The World Health Organization:  www.who.int .

The recommendations on self-management of travellers' diarrhoea are largely based on expert opinion in a World Health Organisation (WHO) publication International Travel and Health [ WHO, 2012 ], the American College of Gastroenterologists guideline Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults [ Riddle et al, 2016 ],  the US consensus Guidelines for the prevention and treatment of travellers' diarrhea: a graded expert panel report [ Riddle, 2017 ], the BMJ Best Practice guideline Traveller's Diarrhoea [ BMJ Best Practice, 2021 ], the Centres for Disease Control (CDC) guideline Travelers' diarrhea -  Preparing International Travelers [ CDC, 2023a ], the guidance on Travellers' diarrhoea from the National Travel Health Network and Centre (NaTHNaC) [ NaTHNaC, 2023 ], as well as a review article Traveler's diarrhea in children: New insights and existing gaps [ Ashkenazi, 2020 ].

Symptomatic treatment for adults

• Expert consensus guidance suggests that, given the concerns regarding potential adverse effects of antibiotics and antimicrobial resistance patterns, increasing fluid intake and treatment with loperamide or bismuth subsalicylate may be sufficient for most people with mild travellers' diarrhoea [ Riddle, 2017 ]. 
• Loperamide reduces the frequency of bowel movements, taking 1–2 hours to reach its therapeutic effect, and appears to have antisecretory properties. It has a well-established safety profile and is usually well-tolerated [ Steffen, 2015 ; Riddle, 2017 ; CDC, 2023a ].
• A systematic review found a small amount of data comparing loperamide with antibiotics and found no proof of antibiotics being more effective for the treatment of travellers' diarrhoea. The review authors therefore advised antibiotics only for severe illness and noted the value of loperamide for symptom control, particularly given increasing antimicrobial resistance [ Laaveri, 2016 ]. 
• Loperamide should be avoided in people with fever or bloody diarrhoea, and/or active inflammatory bowel disease; loperamide can inhibit peristalsis, resulting in complications such as ileus, megacolon, and toxic megacolon [ EMC, 2023a ; CDC, 2023a ; NaTHNaC, 2023 ]

Bismuth subsalicylate

• Bismuth subsalicylate is well tolerated, with usually mild adverse effects in adults,   although it is slower to act than loperamide; may be less effective; cannot be used in some of groups of people, and has the potential for interactions with other medications [ Moore, 2015 ; Giddings, 2016 ; Riddle, 2017 ]. 
• A meta-analysis of data from 11 studies (including the study by DuPont discussed below, total n=840 participants with acute diarrhoea) found that compared to those receiving placebo, people treated with bismuth subsalicylate were 3.7-fold more likely to self-report symptomatic relief [ Brum, 2020 ].

Symptomatic treatment for children not recommended

• Rehydration is the mainstay of self-management for travellers' diarrhoea in young children; parents and carers should be aware that medical assistance should be sought if a child becomes unwell with travellers' diarrhoea, particularly if they are not tolerating fluids or are showing signs of dehydration [ NaTHNaC, 2023 ]. 
• Loperamide is only licensed for use in children older than 12 years and there is limited data on its use in children younger than 12 years old [ EMC, 2023a ]. 
• Bismuth salicylate (Pepto-Bismol ® ) is not licensed for use in children younger than 16 years of age because of the possible association between salicylates and Reye's syndrome [ Ashkenazi, 2020 ; CDC, 2023a ]

When to seek medical assistance

• The recommendations on when to seek medical assistance are in line with guidance issued by the American College of Gastroenterology and an expert panel [ Riddle et al, 2016 ; Riddle, 2017 ], information published by NaTHNaC [ NaTHNaC, 2023 ], and expert opinion [ Leder, 2015 ; Moore, 2015 ; Giddings, 2016 ]  [ Barrett, 2018 ; Ashkenazi, 2020 ].  

When should I consider prescribing a prophylactic antibiotic for travellers' diarrhoea?

• Do not routinely prescribe prophylactic antibiotic treatments for travellers' diarrhoea.
• The risk of the person developing travellers' diarrhoea (see  Assessing risk (before travelling) ).
• The potential harm to the person if they were to develop travellers' diarrhoea.
• The benefits and risks of antibiotic treatment. 
• Access to medical assistance while travelling.
• Have increased susceptibility to infection or are immunocompromised.
• People with chronic gastrointestinal disease (such as Crohn's disease, or ulcerative colitis). 
• People with an ileostomy or colostomy.
• People with other diseases (such as malignancy, type 1 diabetes mellitus, renal disease, stroke, congestive heart failure, or sickle cell disease) in whom a diarrhoeal illness might severely impact on their health.
• Have a history of significant long-term morbidity after an enteric infection (for example, reactive arthritis).
• Are undertaking critical trips in which a short bout of diarrhoea could severely impact the purpose of the trip (for example, athlete, politician, professional musician, lecturer).
• May not have access to adequate medical treatment if they experience complicated travellers' diarrhoea.

The recommendations on when to consider prophylactic antibiotics for travellers' diarrhoea are largely based on expert opinion in a World Health Organisation (WHO) publication International Travel and Health [ WHO, 2012 ], the American College of Gastroenterologists guideline Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults [ Riddle et al, 2016 ], the US consensus Guidelines for the prevention and treatment of travellers' diarrhea: a graded expert panel report [ Riddle, 2017 ], the BMJ Best Practice guideline Traveller's Diarrhoea [ BMJ Best Practice, 2021 ], the Centres for Disease Control (CDC) guidelines Travelers' diarrhea -  Preparing International Travelers [ CDC, 2023a ] and Perspectives: Antibiotics in Travelers' Diarrhea - Balancing Benefit & Risk [ CDC.2023 ] as well as the guidance on Travellers' diarrhoea from the National Travel Health Network and Centre (NaTHNaC) [ NaTHNaC, 2023 ].

Avoiding routine prophylaxis

• Antibiotic prophylaxis has been shown in studies to provide up to 90% protection against developing travellers' diarrhoea. However, for most people the potential risks of prophylaxis with antibiotics outweigh the benefits [ CDC, 2023a ].
• For most people, travellers' diarrhoea is mild and self-limiting.
• Antibiotic prophylaxis offers no protection against non-bacterial causes of travellers' diarrhoea (such as viruses and parasites).
• Removal of normally protective microflora from the bowel with prophylactic antibiotics can increase the risk of infection with resistant bacteria.
• Use of prophylactic antibiotics reduces the choices for treatment if required for travellers' diarrhoea.
• Taking antibiotic prophylaxis may give the traveller a false sense of security, which might lead to neglect of food and water precautions.
• The increasing prevalence of antibiotic resistance is of concern (including to fluoroquinolones).
• No antibiotics are licensed in the UK for the prophylaxis of travellers' diarrhoea.
• Antibiotic treatment can lead to adverse effects and routine use of antibiotics for prophylaxis could expose the person to risks greater than that of the illness.

When to consider prophylaxis

The groups of travellers for whom antibiotic prophylaxis may be considered are based on recommendations from the WHO [ WHO, 2012 ], the CDC [ CDC, 2023a ], a BMJ Best Practice guideline [ BMJ Best Practice, 2021 ] an expert panel report [ Riddle, 2017 ], as well as in a number of review articles [ Barrett, 2016 ; Giddings, 2016 ; DuPont, 2017 ; Taylor, 2017 ; Barrett, 2018 ; Ashkenazi, 2020 ].

• CKS notes that there is some inconsistency in the expert opinion relating to groups of people who may be eligible for prophylaxis.

Seeking specialist advice about prophylaxis

• Planning prophylactic treatment is complex due to the large number of potential pathogens, their geographical variation and resistance patterns, and case-specific factors including comorbidities [ Zaidi and Wine, 2015 ].
• Fluoroquinolones were historically used as the first-line choice for prophylaxis. However, resistance among Campylobacter and Shigella species has been observed globally and fluoroquinolones are associated with cartilage damage, tendon rupture, and C. difficile -associated diarrhoea [ CDC, 2023a ]. In addition, use of fluoroquinolones for prophylaxis limits therapeutic options if travellers' diarrhoea develops [ Taylor, 2017 ].   
• Rifaximin is a non-absorbable antibiotic for which there is evidence of efficacy (although it does not prevent all cases of travellers' diarrhoea), with a favourable safety profile. It is not associated with antimicrobial resistance in travellers and does not appear to modify the gut microflora, but Campylobacter is not susceptible, meaning it only offers moderate protection in South and South East Asia [ Riddle et al, 2016 ; Riddle, 2017 ; Taylor, 2017 ].
• Azithromycin is lacking an evidence base to support its use as a prophylactic agent for travellers' diarrhoea. It is also useful as a therapeutic option for travellers' diarrhoea, particularly in South and South East Asia, and in cases of dysentery,  [ Leder, 2015 ; Giddings, 2016 ; Riddle, 2017 ; Taylor, 2017 ; Barrett, 2018 ].  
• Taking these factors into account, along with the uncertainty regarding the overall benefit of prophylactic antibiotic treatment, and the inconsistent opinion on which groups of people are eligible for prophylaxis, CKS has recommended seeking specialist advice if considering prescribing antibiotic prophylaxis for the prevention of travellers' diarrhoea.

When should I prescribe a 'stand-by' antibiotic for treatment of travellers' diarrhoea?

• Do not routinely prescribe 'stand-by' (to be used if affected) treatments for travellers' diarrhoea.
• Travelling to high-risk locations (especially where access to medical assistance is poor or not available, or there is doubt about the safety and purity of antibiotics available at their destination). 
• At high risk of severe illness.
• The National Travel Health Network and Centre (NaTHNaC) provides a telephone advice line for health professionals advising travellers with complex itineraries or specialist health needs. For more information, see the NaTHNaC website ( www.nathnac.net ).

The recommendations on when to consider 'stand-by' antibiotic treatment for travellers' diarrhoea are largely based on expert opinion in the American College of Gastroenterologists guideline Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults [ Riddle et al, 2016 ], the US consensus Guidelines for the prevention and treatment of travellers' diarrhea: a graded expert panel report [ Riddle, 2017 ], the BMJ Best Practice guideline Traveller's Diarrhoea [ BMJ Best Practice, 2021 ], the Centres for Disease Control (CDC) guidelines Travelers' diarrhea -  Preparing International Travelers [ CDC, 2023a ] and Perspectives: Antibiotics in Travelers' Diarrhea - Balancing Benefit & Risk [ CDC.2023 ] as well as the guidance on Travellers' diarrhoea from the National Travel Health Network and Centre (NaTHNaC) [ NaTHNaC, 2023 ].

Not routinely offering a 'stand-by' antibiotic

• Most cases of travellers' diarrhoea are mild and self-limiting and will resolve without treatment [ Giddings, 2016 ; Riddle, 2017 ].
• Risks of antibiotic treatment for travellers' diarrhoea include changes to the host microbiome, and the acquisition of multidrug resistant bacteria. In particular, travellers to South and Southeast Asia who take antibiotics for travellers' diarrhoea are at risk for colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE), which may be harmful to some, for example older people and those prone to urinary tract infections [ CDC.2023 ]. 
• NaTHNaC advises that since travellers who take antibiotics may acquire organisms that are resistant to antibiotics such multi-drug resistant (MDR) Enterobacteriaceae or Clostridium difficile , the prescribing of antibiotics for standby treatment of travellers' diarrhoea should be carefully considered. Groups that may be eligible include people at high risk of developing severe illness, or those visiting high-risk areas in remote locations where access to medical care is limited [ NaTHNaC, 2023 ]. 

Seeking specialist advice if considering a 'stand-by' antibiotic

• Azithromycin — although it is not licensed for the treatment of travellers' diarrhoea [ EMC, 2023b ],   azithromycin can be useful if there is severe travellers' diarrhoea, dysentery, high fever, travel to south and south East Asia, and if rifaximin has been used as prophylaxis [ Leder, 2015 ; Riddle, 2017 ; Barrett, 2018 ; CDC, 2023a ].   Azithromycin is well-tolerated by most people, and has a more convenient dosing schedule compared with quinolones [ Leder, 2015 ; Riddle, 2017 ]. Prescribers should note, however, that enteropathogens with increased azithromycin resistance have been documented in several countries [ CDC, 2023a ].
• Rifaximin — this antibiotic is licensed for the treatment of travellers' diarrhoea that is not associated with fever, bloody diarrhoea, blood or leucocytes in the stools [ EMC, 2020 ]. Although there is evidence that rifaximin is effective for treating travellers' diarrhoea compared with placebo and has similar efficacy to fluoroquinolones in non-invasive travellers' diarrhoea [ Steffen, 2015 ; Riddle, 2017 ], it is not effective for treating diarrhoea caused by invasive enteric pathogens such as Salmonella, Shigella, or Campylobacter [ EMC, 2020 ].
• Note: although fluoroquinolones were historically first-line therapy for empiric treatment of travellers; diarrhoea, or to treat specific pathogens, there is increasing fluoroquinolone resistance in Campylobacter, Shigella , and Salmonella species, particularly in South and South East Asia, where a significant proportion of travellers' diarrhoea is due to Campylobacter  [ Leder, 2015 ; Riddle, 2017 ; Taylor, 2017 ; CDC, 2023a ]. In addition, the prescribing of fluoroquinolones is now not generally recommended due to risks of multiple adverse reactions including aortic tears, hypoglycaemia, mental health side effects, and tendinitis and tendon rupture [ CDC, 2023a ; NaTHNaC, 2023 ].

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