Travelers' diarrhea is the most predictable travel-related illness and affects 30%-70% of international travelers, depending on destination, season of travel, and other factors. Although most cases of travelers' diarrhea are self-limited and mild to moderate in severity, diarrhea can limit a tourist's itinerary or business activities. Consequently, travelers, particularly in developing countries, are frequently prescribed an antibiotic to self-treat diarrhea, should it develop.
In recent years, research showing antibiotic-mediated disruption of the microbiome and subsequent colonization with resistant organisms has raised concerns about travelers as vehicles for spreading resistance globally as well as possible individual health consequences of acquisition of these resistant organisms.
The International Society of Travel Medicine convened a group of experts on travelers' diarrhea to review the available evidence and produce clinically relevant and useful recommendations on the management of travelers’ diarrhea. Each recommendation was graded according to its strength and the quality of supporting evidence. Clinicians can refer to the full guidelines for additional information on the recommendations and supporting evidence.
For the purpose of these recommendations, the expert panel used the following functional impact definitions to classify travelers' diarrhea:
- Mild: diarrhea that is tolerable, not distressing, and does not interfere with planned activities
- Moderate: diarrhea that is distressing or interferes with planned activities
- Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools) is considered severe
- Persistent: diarrhea lasting 2 weeks or longer
New Recommendations
Prophylaxis for Travelers' Diarrhea
- Antimicrobial prophylaxis should not be used routinely in travelers (strong recommendation, low/very low level of evidence).
- Antimicrobial prophylaxis should be considered for travelers at high risk for health-related complications of travelers' diarrhea (strong recommendation, low/very low level of evidence).
- Bismuth subsalicylate (BSS) may be considered for any traveler to prevent travelers' diarrhea (strong recommendation, high level of evidence). BSS has been studied using four divided doses of either 2.1g/day or 4.2g/day (with meals and at bedtime). A lower divided dose of 1.05g/day has also been shown to be preventive, although it is unclear whether it is as effective as the higher doses.
- When antimicrobial prophylaxis is indicated, rifaximin is recommended for all regions (strong recommendation, moderate level of evidence).
- Fluoroquinolones are not recommended for prophylaxis of travelers' diarrhea (strong recommendation, low/very low level of evidence).
Therapy for Mild Travelers' Diarrhea
- Antibiotic treatment is not recommended in patients with mild travelers' diarrhea (strong recommendation, moderate level of evidence).
- Loperamide or BSS may be considered to treat mild travelers' diarrhea (strong recommendation, moderate level of evidence). The loperamide starting dose is 4mg, followed by an additional 2mg after each additional loose or liquid stool, up to 16mg/day.
Therapy for Moderate Travelers' Diarrhea
- Antibiotics may be used to treat moderate travelers' diarrhea (weak recommendation, moderate level of evidence).
- Fluoroquinolones may be used to treat moderate travelers' diarrhea (strong recommendation, moderate level of evidence). However, emergence of resistance to this class of drug, particularly in Southeast Asia, combined with the potential for reduced diversity of intestinal microbiota (dysbiosis) and adverse musculoskeletal consequences (tendon rupture), contribute uncertainties to the risk-benefit assessment, and the guideline authors did not unanimously grade this recommendation.
- Azithromycin may be used to treat moderate travelers' diarrhea (strong recommendation, high level of evidence).
- Rifaximin may be used to treat moderate travelers' diarrhea (weak recommendation, moderate level of evidence). Clinicians should exercise caution when providing rifaximin for empiric therapy for moderate diarrhea in regions or with itineraries in which the risk for invasive pathogens is high.
- Loperamide may be used as adjunctive therapy for moderate to severe travelers' diarrhea (strong recommendation, high level of evidence).
- Loperamide may be considered for use as monotherapy in moderate travelers' diarrhea (strong recommendation, high level of evidence)
Therapy for Severe Travelers' Diarrhea
- Antibiotics should be used to treat severe travelers' diarrhea (strong recommendation, high level of evidence).
- Azithromycin is preferred to treat severe travelers' diarrhea, including dysentery (strong recommendation, moderate level of evidence).
- Fluoroquinolones may be used to treat severe, nondysenteric travelers' diarrhea (weak recommendation, moderate level of evidence).
- Rifaximin may be used to treat severe, nondysenteric travelers' diarrhea (weak recommendation, moderate level of evidence).
- Single-dose antibiotic regimens may be used to treat moderate or severe travelers' diarrhea (strong recommendation, high level of evidence). If symptoms have not resolved after 24 hours, travelers should be told to continue daily dosing for up to 3 days.
Follow-up and Diagnostic Testing
- Microbiologic testing is recommended in returning travelers with severe or persistent symptoms or in those who do not respond to empiric therapy (strong recommendation, low/very low level of evidence).
- Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis (ungraded). No published studies show that using these tests improves patient outcomes.
Additional Consensus Statements (Ungraded)
- The evidence is insufficient to recommend the use of commercially available prebiotics or probiotics to prevent or treat travelers' diarrhea.
- Studies are needed on changes in the gut microbiome in travelers with and without diarrhea to clarify the benefits and harms of current and novel preventive, diagnostic, and therapeutic approaches.
- There is an incrementally increasing association of travel, travelers' diarrhea, antibiotic use. and the acquisition of multidrug-resistant bacteria. Pretravel counseling should include information about this risk, balanced against the potential benefits of antibiotic use.
Summary for Clinicians
The management of travelers' diarrhea is an unusual clinical scenario in which the traveler is expected to diagnose and treat his or her own illness. Conveying complicated guidelines to travelers is a challenge in the context of an already complex pretravel consultation. The following take-home points can guide the provider and be discussed with the traveler:
- Most, if not all, travelers to destinations in developing countries should be provided with loperamide and an antibiotic for self-treatment.
- If the traveler is going to Southeast Asia, the antibiotic should be azithromycin. A fluoroquinolone, azithromycin, or rifaximin can be used in other regions. If rifaximin is given as a first-line agent, a second prescription for azithromycin should be given in case of dysentery or febrile diarrhea.
- The traveler should be advised that if the illness does not affect his or her travel, to stay hydrated and consider managing symptoms with loperamide.
- The traveler should be advised that if the illness does not affect his or her travel, to stay hydrated and consider managing symptoms with loperamide.
- If the illness is disruptive (for example, keeps the traveler confined to a hotel room), the traveler should start antibiotics and add loperamide if expeditious symptom relief is desired.
- If symptoms do not improve (or if they worsen) within 24-36 hours of beginning antibiotic therapy, the traveler may need to seek medical attention.
- Prophylaxis should be considered only for high-risk groups (underlying health condition or performance-critical occupation or itinerary). Rifaximin is the first choice, and BSS is a second option.
- If rifaximin is used as prophylaxis, azithromycin should be provided to treat breakthrough travelers' diarrhea.
