travellers diarrhoea cdc

• 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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• Section 5 - Diphtheria
• Section 5 - Helicobacter pylori

Escherichia coli , Diarrheagenic

Cdc yellow book 2024.

Author(s): Jennifer Collins, Danielle Tack, Talia Pindyck, Patricia  Griffin

Infectious Agent

Transmission, epidemiology, clinical presentation.

INFECTIOUS AGENT:   Escherichia coli (diarrheagenic)

TRAVELER CATEGORIES AT GREATEST RISK FOR EXPOSURE & INFECTION

PREVENTION METHODS

Follow safe food and water precautions

DIAGNOSTIC SUPPORT

Escherichia coli are gram-negative bacteria that inhabit the gastrointestinal tract. Most types do not cause illness, but 5 pathotypes are associated with diarrhea: enterotoxigenic E. coli (ETEC), Shiga toxin–producing E. coli (STEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), and enteroinvasive E. coli (EIEC). In addition, diffusely adherent E. coli (DAEC) might also be associated with diarrhea. Pathotypes that are common causes of urinary tract infections, bloodstream infections, and meningitis are not covered here.

E. coli serotypes are determined by surface antigens (O and H), and specific serotypes tend to cluster within specific pathotypes. Pathotype determination typically is based on testing for virulence genes. Some E. coli have virulence genes of >1 pathotype; for example, the O104:H4 strain that caused a 2011 outbreak in Germany produced Shiga toxin and had adherence properties typical of EAEC.

STEC also are called verotoxigenic E. coli (VTEC), and the term enterohemorrhagic E. coli (EHEC) commonly is used to specify STEC strains capable of causing human illness, especially bloody diarrhea and hemolytic uremic syndrome (HUS).

Diarrheagenic E. coli pathotypes can be passed in the feces of humans and other animals. Transmission occurs through the fecal–oral route, via consumption of contaminated food or water, and through person-to-person contact, contact with animals or their environment, and swimming in untreated water. Humans constitute the main reservoir for non-STEC pathotypes that cause diarrhea in humans. The intestinal tracts of animals, especially cattle and other ruminants, are the primary reservoirs of STEC.

The 2010 World Health Organization (WHO) Global Burden of Foodborne Diseases report estimated ≈111 million illnesses and ≈63,000 deaths caused by diarrheagenic E. coli globally each year. Rates of infection vary by region, and certain types of diarrheagenic E. coli infections, mainly ETEC, are associated with travel to low- and middle-income countries. The incidence of travel-associated diarrhea caused by E. coli is likely underestimated because many travelers do not seek medical care or have stool testing performed, particularly if diarrhea is non-bloody, as commonly occurs with ETEC infection. Moreover, many clinical laboratories do not use methods that can detect diarrheagenic E. coli other than STEC in stool samples.

Risk for travelers’ diarrhea can be divided into 3 levels, according to the destination country. Low-risk countries include Australia, Canada, Greenland, Japan, New Zealand, the United States, and countries in northern and western Europe. Intermediate-risk countries include Argentina, Brazil, Chile, Morocco, Portugal, South Africa, Thailand (in Bangkok, Chiang Mai, and Phuket; risk to travelers going to rural areas is likely greater), Uruguay, and most countries in the Caribbean, eastern Europe, and the Middle East. High-risk countries include Afghanistan, Burma (Myanmar), the Indian subcontinent, Indonesia, Iran, Malaysia, Mexico, Papua New Guinea, most countries in Africa, and countries in Central America and northern South America, including Bolivia and Paraguay.

STEC infections are most commonly reported in industrialized countries, and ≈85% of STEC infections among international travelers are caused by non-O157 serotypes. Additional information about travelers’ diarrhea is available in Sec. 2, Ch. 6, Travelers’ Diarrhea .

Diarrheagenic E. coli infections, other than STEC, have incubation periods ranging from 8 hours to 3 days. The median incubation period of STEC infection is 3–4 days, with a range of 1–10 days. Clinical manifestations of diarrheagenic E. coli vary by pathotype (see Table 5-02 ). Table 5-02 Mechanism of pathogenesis & typical clinical syndrome of Escherichia coli pathotypes

Table 5-02 Mechanism of pathogenesis & typical clinical syndrome of Escherichia coli pathotypes

Abbreviations: DAEC, diffusely adherent Escherichia coli; EAEC, enteroaggregative E. coli ; EIEC, enteroinvasive E. coli ; EPEC, enteropathogenic E. coli ; ETEC, enterotoxigenic E. coli ; STEC, Shiga toxin–producing E. coli .

Diagnostic testing is not usually recommended for uncomplicated travelers’ diarrhea unless treatment is indicated. Until recently, diarrheagenic E. coli other than STEC could not be distinguished from non-pathogenic E. coli in stool using routine tests in clinical laboratories. Commercial molecular tests have increasingly become available and can identify ETEC, EPEC, EAEC, and EIEC through detection of virulence genes.

Consider several caveats when interpreting results of such tests. The combination of virulence genes that confer pathogenicity has not been determined for all pathotypes, and E. coli sometimes have virulence genes from >1 pathotype due to transfer of mobile genetic elements. Some studies have identified some genes, including the eae gene used to diagnose EPEC, at a similar frequency in stools from healthy people as from those with acute diarrhea. Identification of 2 virulence genes in a specimen does not mean they are carried by the same organism. Finally, molecular tests detect genetic material, which does not always correspond to the presence of viable organisms.

Using PCR or whole-genome sequence analysis to facilitate recognition of specific E. coli pathotypes, state public health and Centers for Disease Control and Prevention laboratories can assist in outbreak investigations. When STEC infection is suspected, stool samples should be cultured for E. coli O157 and simultaneously tested for Shiga toxins or the genes that encode them. See more information . Send all presumptive E. coli O157 isolates and Shiga toxin–positive specimens to a public health laboratory for further characterization and for outbreak detection. Rapid, accurate diagnosis of STEC infection is important because early clinical management decisions can affect patient outcomes, and early detection can help prevent further transmission.

Maintenance of hydration and electrolyte balance with oral rehydration is important, especially in patients with vomiting or profuse diarrhea. Travelers with mild non-bloody diarrhea can use loperamide to decrease the frequency of loose stools. Travelers with moderate illness can consider self-treatment with an antibiotic, and those with bloody diarrhea or severe illness (that keeps them confined to their room) should generally receive antibiotic therapy. Travelers can use loperamide as an adjunctive therapy to antibiotics taken for moderate or severe travelers’ diarrhea.

Azithromycin is preferred for bloody diarrhea or severe illness and is an option for moderate non-bloody diarrhea. Fluoroquinolones (e.g., ciprofloxacin) can be effective, but resistant strains are increasing in frequency, particularly in Asia; other agents are also preferred because fluoroquinolones have been associated with adverse effects, including tendinopathies, QT interval prolongation (a cardiac conduction abnormality), and Clostridioides difficile enterocolitis.

If treatment with azithromycin or a fluoroquinolone does not improve the condition within 24 hours, travelers should continue the antibiotic for no longer than 3 days. A 3-day course of rifaximin is effective for some non-bloody diarrheal illnesses. Administering certain antimicrobial agents to patients whose clinical syndrome suggests STEC infection could increase their risk of developing HUS ( Table 5-02 ). Studies of children with STEC O157 infection have shown that early use of intravenous fluids (within the first 4 days of diarrhea onset) might decrease the risk of oligoanuric renal failure.

Antimicrobial-resistant E. coli are increasing worldwide. Carefully weigh the decision to use an antibiotic against the severity of illness; the possibility that the pathogen is resistant; and the risk for adverse reactions (e.g., HUS, rash, other manifestations of allergy), antibiotic-associated colitis, and vaginal yeast infection. Some studies suggest that loperamide combined with antibiotics can be used safely in many patients. Due to a potential risk for complications, including toxic megacolon and HUS, avoid treating bloody diarrhea or STEC infection solely with antimotility drugs.

No vaccine is available for E. coli infection. Although bismuth subsalicylate and certain antimicrobial agents (e.g., fluoroquinolones, rifaximin) can prevent E. coli diarrhea, chemoprophylaxis is not recommended for most travelers. Furthermore, antimicrobial drug use can adversely affect the intestinal microbiota and increase susceptibility to gut infections.

Remind travelers of the importance of adhering to food and water precautions (see Sec. 2, Ch. 8, Food & Water Precautions ), and instruct travelers about the importance of handwashing. Because soap and water might not be readily available, travelers should consider taking hand sanitizer with ≥60% alcohol with them when they travel.

CDC website: E. coli

The following authors contributed to the previous version of this chapter: Alison Winstead, Jennifer C. Hunter, Patricia M. Griffin

Bibliography

Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, et al. Epidemic profile of Shiga-toxin–producing Escherichia coli O104: H4 outbreak in Germany. New Engl J Med. 2011;365(19):1771–80.

Guiral E, Gonçalves Quiles M, Muñoz L, Moreno-Morales J, Alejo-Cancho I, Salvador P, et al. Emergence of resistance to quinolones and β-lactam antibiotics in enteroaggregative and enterotoxigenic Escherichia coli causing traveler’s diarrhea. Antimicrob Agents Chemother. 2019;63(2):e01745-18.

Havelaar AH, Kirk MD, Torgerson PR, Gibb HJ, Hald T, Lake RJ, et al. World Health Organization global estimates and regional comparisons of the burden of foodborne disease in 2010. PLoS Med. 2015;12(12):e1001923.

Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli . Nat Rev Microbiol. 2004;2(2):123–40.

Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013;382(9888):209–22.

Mintz ED. Enterotoxigenic Escherichia coli : outbreak surveillance and molecular testing. Clin Infect Dis. 2006;42(11):1518–20.

Mody RK, Griffin PM. Editorial commentary: increasing evidence that certain antibiotics should be avoided for Shiga toxin–producing Escherichia coli infections: more data needed. Clin Infect Dis. 2016;62(10):1259–61.

Riddle MS, Connor BA, Beeching NJ, DuPont HL, Hamer DH, Kozarsky P, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. J Travel Med. 2017;24(suppl_1):S63–80.

Shane AL, Mody RK, Crump JA, Tarr PI, Steiner TS, Kotloff K, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65(12):e45–80.

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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.

Traveler’s Diarrhea

• Symptoms and Signs |
• Diagnosis |
• Treatment |
• Prevention |
• Key Points |
• More Information |

Traveler’s diarrhea is gastroenteritis that is usually caused by bacteria endemic to local water. Symptoms include vomiting and diarrhea. Diagnosis is mainly clinical. Treatment is with replacement fluids and sometimes antibiotics for moderate to severe diarrhea.

(See also Overview of Gastroenteritis and see the Center for Disease Control and Prevention’s [CDC] information for preparing international travelers for travelers’ diarrhea .)

Etiology of Traveler's Diarrhea

Traveler’s diarrhea may be caused by any of several bacteria, viruses, or, less commonly, parasites.

The most common cause of traveler's diarrhea is

Enterotoxigenic Escherichia coli ( E. coli )

E. coli is common in the water supplies of areas that lack adequate purification. Infection is common among people traveling to low-resource countries.

Norovirus gastroenteritis has been a particular problem on some cruise ships.

Both food and water can be the source of infection. Travelers who avoid drinking local water may still become infected by brushing their teeth with an improperly rinsed toothbrush, drinking bottled drinks with ice made from local water, or eating food that is improperly handled or washed with local water. People taking medications that decrease stomach acid (antacids, H2 blockers, and proton pump inhibitors) are at risk of more severe illness.

Symptoms and Signs of Traveler's Diarrhea

Nausea, vomiting, hyperactive bowel sounds, abdominal cramps, and diarrhea begin 12 to 72 hours after ingesting contaminated food or water. Severity is variable. Some people develop fever and myalgias. Diarrhea is rarely bloody.

Most cases are mild and self-limited, although dehydration can occur, especially in warm climates.

Diagnosis of Traveler's Diarrhea

Clinical evaluation

Specific diagnostic measures are usually not necessary. However, fever, severe abdominal pain, and bloody diarrhea suggest more serious disease and should prompt immediate evaluation.

Treatment of Traveler's Diarrhea

Fluid replacement

Sometimes antidiarrheal (antimotility) medications

Antibiotics (eg, ciprofloxacin , azithromycin ) for moderate to severe diarrhea

The mainstay of treatment of traveler's diarrhea is fluid replacement and an antidiarrheal medication such as loperamide

Antidiarrheal medications should not be used in adults with suspected C. difficile or E. coli O157:H7 infection (eg, with recent antibiotic use, bloody diarrhea, heme-positive stool, or diarrhea with fever) or in children, particularly those < 2 years. Iodochlorhydroxyquin, which may be available in some low- and middle-income countries, should not be used because it may cause neurologic damage.

Pearls & Pitfalls

Generally, antibiotics are not necessary for mild diarrhea. However, in patients with moderate to severe diarrhea ( ≥ Campylobacter 2017 guidelines for the prevention and treatment of travelers' diarrhea .)

Prevention of Traveler's Diarrhea

Travelers should dine at restaurants with a reputation for safety and avoid foods and beverages from street vendors. They should consume only cooked foods that are still steaming hot, fruit that can be peeled, and carbonated beverages without ice served in sealed bottles (bottles of noncarbonated beverages can contain tap water added by unscrupulous vendors); uncooked vegetables (particularly including salsa left out on the table) should be avoided. Buffets and fast food restaurants pose an increased risk.

Traveler's diarrhea is usually caused by enterotoxigenic E. coli , but viruses, parasites, and other bacteria may be involved.

Diagnosis is clinical and testing is not usually needed unless bloody diarrhea, fever, or abdominal pain is present.

Prevention is the best measure and involves careful selection of foods and beverages; prophylactic antibiotics are not routinely used except for patients with immunocompromise.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Centers for Disease Control and Prevention: Preparing international travelers for travelers’ diarrhea

Expert panel: Guidelines for the prevention and treatment of travelers' diarrhea (2017)

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Traveller's diarrhoea

• Overview  
• Theory  
• Diagnosis  
• Management  
• Follow up  
• Resources  

Traveller's diarrhoea is a common problem among travellers, typically caused by the consumption of contaminated food or water. Predominantly caused by bacteria.

Prevention strategies include careful selection of food and beverages, though these are not fail-safe. Prophylactic antibiotics are not recommended for most travellers.

Management is self-diagnosis while still travelling, followed by hydration, medicine for symptom relief, and possibly, antibiotics. Antibiotic therapy is generally reserved for moderate to severe infections.

In healthy patients, resolution is typically within 3 to 5 days even without antibiotic treatment.

Traveller's diarrhoea (TD) is defined as ≥3 unformed stools in 24 hours accompanied by at least 1 of the following: fever, nausea, vomiting, cramps, tenesmus, or bloody stools (dysentery) during a trip abroad, typically to a low- or middle-income country. It is usually a benign self-limited illness lasting 3 to 5 days.

History and exam

Key diagnostic factors.

• presence of risk factors
• diarrhoea (with or without tenesmus), cramping, nausea, and vomiting
• dysentery (blood and fever)
• persistent diarrhoea >14 days

Other diagnostic factors

• diarrhoea without illness

Risk factors

• travel to a high-risk destination
• age <30 years
• decreased stomach acidity
• prior TD susceptibility
• chronic disease, immunocompromise
• travellers with prior residence in developing country visiting friends and relatives
• travel during hot and wet seasons

Diagnostic investigations

1st investigations to order.

• stool culture and sensitivity
• stool occult blood
• multi-pathogen molecular diagnostic (polymerase chain reaction)
• stool ova and parasite examination

Investigations to consider

• protozoal stool antigens
• Clostridium difficile stool toxin
• colonoscopy, endoscopy, and biopsy
• haematology, blood chemistries, serology

Treatment algorithm

Pre-travel prophylaxis, non-pregnant adults: mild diarrhoea, non-pregnant adults: moderate diarrhoea, non-pregnant adults: severe diarrhoea, contributors, mark riddle, md, mph&tm, drph, c trop med, certificate in travel health.

Professor and Chair

Department of Preventive Medicine & Biostatistics

Uniformed Services University of the Health Sciences

Disclosures

MR has given talks on the management of traveller's diarrhoea for the International Society of Travel Medicine (ISTM), CDC Foundation, American College of Gastroenterology (ACG), and American College of Preventive Medicine. MR has led the development of guidelines for traveller's diarrhoea for the ISTM, ACG, and the US Department of Defense. This work has been unpaid but support for travel has been accepted. MR is an author of several references cited in this topic.

Acknowledgements

Dr Mark Riddle would like to gratefully acknowledge Professor Gregory Juckett, the previous contributor to this topic.

GJ declares that he has no competing interests.

Peer reviewers

Andrea summer, md.

Assistant Professor of Pediatrics

Medical University of South Carolina

AS declares that she has no competing interests.

Phil Fischer, MD

Professor of Pediatrics

Department of Pediatric and Adolescent Medicine

Mayo Clinic

PF is an author of a reference cited in this topic.

Differentials

• Irritable bowel syndrome
• Secondary disaccharidase (or other dietary) deficiency
• Malabsorptive conditions
• CDC Yellow Book: travelers' diarrhea
• 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea

Patient leaflets

Diarrhoea in adults

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Travelers’ Diarrhea

Travelers’ diarrhea (TD) is the most predictable travel-related illness. Attack rates range from 30% to 70% of travelers, depending on the destination and season of travel. Traditionally, it was thought that TD could be prevented by following simple recommendations such as “boil it, cook it, peel it, or forget it,” but studies have found that people who follow these rules may still become ill. Poor hygiene practice in local restaurants is likely the largest contributor to the risk for TD.

TD is a clinical syndrome that can result from a variety of intestinal pathogens. Bacterial pathogens are the predominant risk, thought to account for up to 80%–90% of TD. Intestinal viruses may account for at least 5%–15% of illnesses, although multiplex molecular diagnostic assays increase their detection. Infections with protozoal pathogens are slower to manifest symptoms and collectively account for approximately 10% of diagnoses in longer-term travelers. What is commonly known as “food poisoning” involves the ingestion of preformed toxins in food. In this syndrome, vomiting and diarrhea may both be present, but symptoms usually resolve spontaneously within 12 hours.

Infectious Agents

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 are also commonly found in cases of TD. There is increasing discussion of Aeromonas spp., Plesiomonas spp., and newly recognized pathogens ( Acrobacter, Larobacter , enterotoxigenic Bacteroides fragilis ) as potential causes of TD as well. Viral diarrhea can be caused by a number of pathogens, including norovirus, rotavirus, and astrovirus.

Giardia is the main protozoal pathogen found in TD. Entamoeba histolytica is a relatively uncommon cause of TD, and Cryptosporidium is also relatively uncommon. The risk for Cyclospora is highly geographic and seasonal: the most well-known risks are in Nepal, Peru, Haiti, and Guatemala. Dientamoeba fragilis is a flagellate occasionally associated with diarrhea in travelers. Most of the individual pathogens are discussed in their own sections in Chapter 4, and diarrhea in returned travelers is discussed in Chapter 11.

Risk for Travelers

TD occurs equally in male and female travelers and 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 may occur during a single trip. A cohort of expatriates residing in Kathmandu, Nepal, experienced an average of 3.2 episodes of TD per person in their first year. In more temperate regions, there may be seasonal variations in diarrhea risk. In south Asia, for example, much higher TD attack rates are reported during the hot months preceding the monsoon.

In environments in warmer climates where large numbers of people do not have access to plumbing or latrines, the amount of stool contamination in the environment will be higher and more accessible to flies. Inadequate electrical capacity may lead to frequent blackouts or poorly functioning refrigeration, which can result in unsafe food storage and an increased risk for disease. Lack of safe water may lead to contaminated foods and drinks prepared with such water; inadequate water supply may lead to shortcuts in cleaning hands, surfaces, utensils, and foods such as fruits and vegetables. In addition, handwashing may not be a social norm and could be an extra expense; thus there may be no handwashing stations in food preparation areas. In destinations in which effective food handling courses have been provided, the risk for TD has been demonstrated to decrease. However, even in developed countries, pathogens such as Shigella sonnei have caused TD linked to handling and preparation of food in restaurants.

Clinical Presentation

Bacterial and viral TD presents with the sudden onset of bothersome symptoms that can range from mild cramps and urgent loose stools to severe abdominal pain, fever, vomiting, and bloody diarrhea, although with norovirus vomiting may be more prominent. Protozoal diarrhea, such as that caused by Giardia intestinalis or E. histolytica , generally has a more gradual onset of low-grade symptoms, with 2–5 loose stools per day. The incubation period between exposure and clinical presentation can be a clue to the etiology:

• Bacterial toxins generally cause symptoms within a few hours.
• Bacterial and viral pathogens have an incubation period of 6–72 hours.
• Protozoal pathogens generally have an incubation period of 1–2 weeks and rarely present in the first few days of travel. An exception can be Cyclospora cayetanensis , which can present quickly in areas of high risk.

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 gastroenteritis can lead to persistent gastrointestinal symptoms, even in the absence of continued infection (see Chapter 11 , Persistent Diarrhea in Returned Travelers). This presentation is commonly referred to as postinfectious irritable bowel syndrome. Other postinfectious sequelae may include reactive arthritis and Guillain-Barré syndrome.

For travelers to high-risk areas, several approaches may be recommended that can reduce, but never completely eliminate, the risk for TD. These include following instructions regarding food and beverage selection, using agents other than antimicrobial drugs for prophylaxis, using prophylactic antibiotics, and carefully washing hands with soap where available. Carrying small containers of alcohol-based hand sanitizers (containing ≥60% alcohol) may make it easier for travelers to clean their hands before eating when handwashing is not possible. No vaccines are available for most pathogens that cause TD, but travelers should refer to the Cholera, Hepatitis A, and Typhoid & Paratyphoid Fever sections in Chapter 4 regarding vaccines that can prevent other foodborne or waterborne infections to which travelers are susceptible.

Food and Beverage Selection

Care in selecting food and beverages can minimize the risk for acquiring TD. See the Food & Water Precautions section in this chapter for CDC’s detailed food and beverage recommendations. Although food and water precautions continue to be recommended, travelers may not always be able to adhere to the advice. Furthermore, many of the factors that ensure food safety, such as restaurant hygiene, are out of the traveler’s control.

Nonantimicrobial Drugs for Prophylaxis

The primary agent studied for prevention of TD, other than antimicrobial drugs, is bismuth subsalicylate (BSS), which is the active ingredient in adult formulations of Pepto-Bismol and Kaopectate. Studies from Mexico have shown that this agent (taken daily as either 2 oz. of liquid or 2 chewable tablets 4 times per day) reduces the incidence of TD by approximately 50%. BSS commonly causes blackening of the tongue and stool and may cause nausea, constipation, and rarely tinnitus.

Travelers with aspirin allergy, renal insufficiency, and gout, and those taking anticoagulants, probenecid, or methotrexate should not take BSS. In travelers taking aspirin or salicylates for other reasons, the use of BSS may result in salicylate toxicity. BSS is not generally recommended for children aged <12 years; however, some clinicians use it off-label with caution to avoid administering BSS to children aged ≤18 years with viral infections, such as varicella or influenza, because of the risk for Reye syndrome. BSS is not recommended for children aged <3 years or pregnant women. Studies have not established the safety of BSS use for periods >3 weeks. Because of the number of tablets required and the inconvenient dosing, BSS is not commonly used as prophylaxis for TD.

The use of probiotics, such as Lactobacillus GG and Saccharomyces boulardii , has been studied in the prevention of TD in small numbers of people. Results are inconclusive, partially because standardized preparations of these bacteria are not reliably available. Studies are ongoing with prebiotics to prevent TD, but data are insufficient to recommend their use. There have been anecdotal reports of beneficial outcomes after using bovine colostrum as a daily prophylaxis agent for TD. However, commercially sold preparations of bovine colostrum are marketed as dietary supplements that are not Food and Drug Administration (FDA) approved for medical indications. Because no data from rigorous clinical trials demonstrate efficacy, there is insufficient information to recommend the use of bovine colostrum to prevent TD.

Prophylactic Antibiotics

Although prophylactic antibiotics can prevent some TD, the emergence of antimicrobial resistance has made the decision of how and when to use antibiotic prophylaxis for TD difficult. Controlled studies have shown that use of antibiotics reduces diarrhea attack rates by 90% or more. The prophylactic antibiotic of choice has changed over the past few decades as resistance patterns have evolved. Fluoroquinolones have been the most effective antibiotics for the prophylaxis and treatment of bacterial TD pathogens, but increasing resistance to these agents among Campylobacter and Shigella species globally limits their potential use. In addition fluoroquinolones are associated with tendinitis and an increased risk of Clostridioides difficile infection, and current guidelines discourage their use for prophylaxis. Alternative considerations include azithromycin, rifaximin, and rifamycin SV.

At this time, prophylactic antibiotics should not be recommended for most travelers. Prophylactic antibiotics afford no protection against nonbacterial pathogens and can remove normally protective microflora from the bowel, increasing the risk of infection with resistant bacterial pathogens. Travelers may become colonized with extended-spectrum β -lactamase (ESBL)–producing bacteria, and this risk is increased by exposure to antibiotics while abroad. Additionally, the use of antibiotics may be associated with allergic or adverse reactions, and prophylactic antibiotics limit the therapeutic options if TD occurs; a traveler relying on prophylactic antibiotics will need to carry an alternative antibiotic to use if severe diarrhea develops despite prophylaxis.

The risks associated with the use of prophylactic antibiotics should be weighed against the benefit of using prompt, early self-treatment with antibiotics when moderate to severe TD occurs, shortening the duration of illness to 6–24 hours in most cases. Prophylactic antibiotics may be considered for short-term travelers who are high-risk hosts (such as those who are immunosuppressed or with significant medical comorbidities) or those who are taking critical trips (such as engaging in a sporting event) without the opportunity for time off in the event of sickness.

Oral Rehydration Therapy

Fluids and electrolytes are lost during TD, and replenishment is important, especially in young children or adults with chronic medical illness. In adult travelers who are otherwise healthy, severe dehydration resulting from TD is unusual unless vomiting is prolonged. Nonetheless, replacement of fluid losses remains an adjunct to other 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.

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

Antimotility Agents

Antimotility agents provide symptomatic relief and are useful therapy in TD. Synthetic opiates, such as loperamide and diphenoxylate, 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-producing pathogens may 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 small children (aged <6 years).

Antibiotics

Antibiotics are effective in reducing the duration of diarrhea by about a day in cases caused by bacterial pathogens that are susceptible to the particular antibiotic prescribed. However, there are concerns about adverse consequences of using antibiotics to treat TD. Travelers who take antibiotics may acquire resistant organisms such as ESBL-producing organisms, resulting in potential harm to travelers—particularly those who are immunosuppressed or women who may be prone to urinary tract infections—and the possibility of introducing these resistant bacteria into the community. In addition, there is concern about the effects of antibiotic use on travelers’ microbiota and the potential for adverse consequences such as Clostridioides difficile infection as a result. These concerns have to be weighed against the consequences of TD and the role of antibiotics in shortening the acute illness and possibly preventing postinfectious sequelae (see Chapter 11 , Persistent Diarrhea in Returned Travelers).

Primarily because of these concerns, an expert advisory panel was convened in 2016 to prepare consensus guidelines on the prevention and treatment of TD. A classification of TD using functional impact for defining severity (Box 2-3 ) was suggested rather than the frequency-based algorithm that has traditionally been used. The guidelines suggest an approach that matches therapeutic intervention with severity of illness, in terms of both safety and effectiveness (Table 2-10 ).

The effectiveness of a particular antimicrobial drug depends on the etiologic agent and its antibiotic sensitivity (Table 2-11 ). As empiric therapy or to treat a specific bacterial pathogen, first-line antibiotics have traditionally been the fluoroquinolones, such as ciprofloxacin or levofloxacin. Increasing microbial resistance to the fluoroquinolones, especially among Campylobacter isolates, may limit their usefulness in many destinations, particularly South and Southeast Asia, where both Campylobacter infection and fluoroquinolone resistance is prevalent. Increasing fluoroquinolone resistance has been reported from other destinations and in other bacterial pathogens, including in Shigella and Salmonella . In addition, the use of fluoroquinolones has been associated with tendinopathies and the development of C. difficile infection. FDA warns that the potentially serious side effects of fluoroquinolones may outweigh their benefit in treating uncomplicated respiratory and urinary tract infections; however, because of the short duration of therapy for TD, these side effects are not believed to be a significant risk.

A potential alternative to fluoroquinolones is azithromycin, although enteropathogens with decreased azithromycin susceptibility have been documented in several countries. Rifaximin has been approved to treat TD caused by noninvasive strains of E. coli . However, since it is often difficult for travelers to distinguish between invasive and noninvasive diarrhea, 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 to be determined.

Single-dose regimens are equivalent to multidose regimens and may be more convenient for the traveler. Single-dose therapy with a fluoroquinolone is well established, both by clinical trials and clinical experience. The best regimen for azithromycin treatment may also be a single dose of 1,000 mg, but side effects (mainly nausea) may limit the acceptability of this large dose. Giving azithromycin as 2 divided doses on the same day may limit this adverse event.

Box 2-3. Travelers’ diarrhea definitions

Mild (acute): diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.

Moderate (acute): diarrhea that is distressing or interferes with planned activities.

Severe (acute): diarrhea that is incapacitating or completely prevents planned activities; all dysentery is considered severe.

Treatment of TD Caused by Protozoa

The most common parasitic cause of TD is Giardia intestinalis , and treatment options include metronidazole, tinidazole, and nitazoxanide (see Chapter 4 , Giardiasis). Although cryptosporidiosis is usually a self-limited illness in immunocompetent people, nitazoxanide can be considered as a treatment option. Cyclosporiasis is treated with trimethoprim-sulfamethoxazole. Treatment of amebiasis is with metronidazole or tinidazole, followed by treatment with a luminal agent such as iodoquinol or paromomycin.

A new therapeutic option is rifamycin SV, which was approved by 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 noninferior to ciprofloxacin in the treatment of TD.

Treatment for Children

Children who accompany their parents on trips to high-risk destinations can contract TD as well, with elevated risk if they are visiting friends and family. Causative organisms include bacteria responsible for TD in adults, as well as viruses including norovirus and rotavirus. The main treatment for TD in children is ORS. Infants and younger children with TD are at higher risk for dehydration, which is best prevented by the early initiation of oral rehydration. Empiric antibiotic therapy should be considered if there is bloody or severe watery diarrhea or evidence of systemic infection. In older children and teenagers, treatment recommendations for TD follow those for adults, with possible adjustments in the dose of medication. Among younger children, macrolides such as azithromycin are considered first-line antibiotic therapy, although some experts now use short-course fluoroquinolone therapy (despite its not being FDA-approved for this indication in children) for travelers aged <18 years. 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 may consume a regular diet. Children in diapers are at risk for developing diaper rash on their buttocks in response to the liquid stool. Barrier creams, such as zinc oxide or 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 Chapter 7 , Traveling Safely with Infants & Children.

Bibliography

• Black RE. Epidemiology of travelers’ diarrhea and relative importance of various pathogens. Rev Infect Dis. 1990 Jan–Feb;12(Suppl 1):S73–9.   [PMID:2406860]
• DeBruyn G, Hahn S, Borwick A. Antibiotic treatment for travelers’ diarrhea. Cochrane Database Syst Rev 2000;3:1–21.
• DuPont HL, Ericsson CD, Farthing MJ, Gorbach S, Pickering LK, Rombo L, et al. Expert review of the evidence base for prevention of travelers’ diarrhea. J Travel Med. 2009 May–Jun;16(3):149–60.   [PMID:19538575]
• Farthing M, Salam MA, Lindberg G, Dite P, Khalif I, Salazar-Lindo E, et al. Acute diarrhea in adults and children: a global perspective. J Clin Gastroenterol. 2013 Jan;47(1):12–20.   [PMID:23222211]
• Kantele A, Lääveri T, Mero S, Vilkman K, Pakkanen S, Ollgren J, et al. Antimicrobials increase travelers’ risk of colonization by extended-spectrum betalactamase producing Enterobacteriaceae. Clin Infect Dis. 2015 Mar 15;60(6):837–46.   [PMID:25613287]
• 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 Jun;54(Suppl 5):S480–7.   [PMID:22572673]
• Mcfarland LV. Meta-analysis of probiotics for the prevention of travelers’ diarrhea. Cochrane Database Syst Rev 2010;Cd003048.
• Raja MK, Ghosh AR. Laribacter hongkongensis: an emerging pathogen of infectious diarrhea. Folia Microbiol. (Praha) 2014 Jul;59 (4):341–7.   [PMID:24481985]
• 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–S19.
• Riddle MS, DuPont HL, Connor BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016 May;111(5):602–22.   [PMID:27068718]
• Shlim DR. Looking for evidence that personal hygiene precautions prevent travelers’ diarrhea. Clin Infect Dis. 2005 Dec 1;41(Suppl 8):S531–5.   [PMID:16267714]
• Steffen R, Hill DR, DuPont HL. Traveler’s diarrhea: a clinical review. JAMA. 2015 Jan 6;313(1):71–80.   [PMID:25562268]
• 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.

Bradley A. Connor

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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

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• Paredes-Paredes M, Flores-Figueroa J, Dupont HL. Advances in the treatment of travelers’ diarrhea. Curr Gastroenterol Rep 2011;13:402–07. Search PubMed
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• Nair D. Travelers’ diarrhea: prevention, treatment, and post-trip evaluation. J Fam Pract 2013;62:356–61. Search PubMed
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• 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
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• 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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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.

Investigation Update on the Silver Nova

Cruise Line : Silversea Cruises

Cruise Ship : Silver Nova

Voyage Dates : March 31–April 16, 2024

Voyage number: SN240331016

Number of passengers who reported being ill during the voyage out of total number of passengers onboard : 28 of 633 (4.42%)

Number of crew who reported being ill during the voyage out of total number of crew onboard : 1 of 538 (0.19%)

Predominant symptom : diarrhea

Causative agent : unknown

Actions : In response to the outbreak, Silversea Cruises and the crew aboard the ship reported the following actions:

• Made announcements to notify onboard passengers and crew of the outbreak, encourage case reporting, and encourage good hand hygiene.
• Isolated ill passengers and crew.
• Increased cleaning and disinfection procedures according to the ship’s outbreak prevention and response plan.

VSP is remotely monitoring the situation, including reviewing the ship’s outbreak response and sanitation procedures.

Note : The gastrointestinal illness cases reported are totals for the entire voyage and do not represent the number of active (symptomatic) gastrointestinal cases at any given port of call or at disembarkation.

Learn how passengers can protect themselves with these  tips for healthy cruising .

• Inspection Reports
• About Inspections
• Cruise Ship Outbreak Updates
• About Noroviruses on Cruise Ships
• VSP Operations Manual   [PDF – 5 MB]
• VSP Construction Guidelines   [PDF – 4 MB]
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Nearly 30 Cruise Ship Passengers In US Mysteriously Fall Ill With Diarrhoea

The "easter-themed" cruise began in peru on march 31 and ended in fort lauderdale, florida, on tuesday..

The cruise ship quarantined its impacted passengers.

Nearly 30 passengers on a luxury cruise ship got sick in a gastrointestinal illness outbreak despite Silversea Cruises being known for its phenomenal cuisine, as per a report in the New York Post . The Centers for Disease Control and Prevention announced on Monday that during the 16-day journey from Peru, at least 28 of the Silver Nova's 633 passengers and one member of the crew reported feeling ill.

The CDC added that the main symptom was diarrhoea. Although the exact source of the outbreak, which has affected about 5 per cent of the passengers on board, is still unknown, the CDC stated that contaminated food or water is the main cause of norovirus outbreaks.

The cruise ship made announcements informing both staff and guests about the outbreak and urged them to report instances and adopt "good hand hygiene." In addition, Silversea reportedly quarantined its impacted passengers and increased cleaning and disinfection procedures. 

"The health and safety of our guests, crew, and the communities we visit are our top priority. To maintain an environment that supports the highest levels of health and safety onboard our ships, we implement rigorous cleaning procedures, many of which far exceed public health guidelines," a spokesperson for Silversea Cruises told The Post in a statement. The "Easter-themed" cruise began in Peru on March 31 and ended in Fort Lauderdale, Florida, on Tuesday.

According to CruiseMapper, the starting price for a double occupancy room on the 16-day adventure was $11,700.

In February, several passengers on board Cunard Cruise Line in the US were struck down with vomiting and diarrhoea, CDC said. According to the press note, at least 123 passengers and 16 crew members travelling on the Queen Victoria reported falling ill since the voyage set off on January 22 from Florida. 

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The cause of the gastrointestinal illness was not known, health officials said, but they added that the main symptoms among those on board the vessel included diarrhoea and vomiting. 

This came weeks after passengers on board a Florida-based cruise ship came down with an unknown illness. Passengers on the cruise ship reported symptoms of gastroenteritis, or the stomach flu, after setting off from Jacksonville. One passenger, Miranda Hill said her bout of illness was so bad that she started hurling blue vomit. "My throw up was bright blue and I have never eaten anything blue and every time I look up blue throw up, it has to deal with a poisoning," she said.  

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