Expert Review of the Evidence Base for Self‐Therapy of Travelers’ Diarrhea

Herbert L. DuPont MD, Charles D. Ericsson MD, Michael J. G. Farthing MD, Sherwood Gorbach MD, Larry K. Pickering MD, Lars Rombo MD, PhD, Robert Steffen MD, Thomas Weinke MD
DOI: 161-171 First published online: 1 May 2009

The most frequent illness among people traveling from industrialized regions to developing countries is travelers’ diarrhea (TD). For all people entering areas known to pose a high risk for TD, medication should be included in the travel kit on trips, which can be taken for self‐therapy of resultant diarrheal illness. Drugs aimed at relief of symptoms, particularly loperamide, are the preferred standard treatment of TD by some professionals in Europe. Travel medicine experts in the United States and many in Europe feel that an antimicrobial agent that cures while shortening the duration of illness represents the mainstay of therapy. Loperamide combined with an appropriate antimicrobial agent will provide the most rapid relief of TD. In the following document, the authors used an evidence base when available to determine the strength and quality of evidence and when data were lacking, the panel of experts provided consensus opinion.

Major findings

Drugs used for symptomatic relief, including bismuth subsalicylate (BSS) and loperamide, decrease the number of unformed stools passed during a bout of TD but may not speed up illness recovery. The majority of authors of this document recommended that for all people traveling from low‐risk to high‐risk regions, one of the three antibacterial drugs should be transported with them for self‐treatment of diarrhea that occurs, given in respective order of development for TD therapy: a fluoroquinolone (ciprofloxacin or levofloxacin), rifaximin, or azithromycin. Azithromycin is preferred for treatment when diarrhea is complicated by dysentery (passage of grossly bloody stools) or by high fever and for use in children with TD. A number of experts would recommend additionally including loperamide in the travel kit for adults with TD as this may accelerate relief of the illness when used with an antimicrobial agent. An uncertain proportion of Europeans feel that it is sufficient to include loperamide alone in the travel kit for routine self‐treatment of TD.


The purpose of this review is to provide available evidence for effectiveness of self‐therapy of TD during international travel. This area is controversial with differing support among specialists for the various known effective drugs and use of drugs in various regions of the world. In the review, these differences of opinion are identified. The risks and benefits of the available approaches are discussed. Recommendations are graded by the strength and quality of evidence (Table 1). When evidence is lacking, the quality of evidence is graded as category III, representing a consensus of expert authors (Table 1).

View this table:
Table 1

Grading of clinical evidence in the therapy of travelers’ diarrhea 101

Strength of evidenceAGood evidence to support a recommendation for use
BModerate evidence to support a recommendation for use
CPoor evidence to support a recommendation
DModerate evidence to support a recommendation against use
EGood evidence to support a recommendation against use
Quality of evidenceIEvidence from ≥1 properly randomized, controlled trial
IIEvidence from ≥1 well‐designed clinical trial without randomization, from case‐controlled analysis of cohort study
IIIConsensus evidence, evidence from one authority or reports of expert committees

Target population

These recommendations are made for travel populations originating from an industrialized country and visiting destinations with suboptimal hygienic conditions in the tropics or subtropics. The travel populations include healthy adult travelers, children, pregnant women, people with underlying illness and immunosuppression, and the elderly. The concepts apply less to infants because unlike other groups, they receive food and drinks safely prepared by caregivers. The target audience for receipt of the material includes nurse‐ and physician‐travel medicine practitioners, primary care physicians, medical students and residents in training, and infectious diseases and tropical medicine specialists.

Desired Outcome and Methods

The authors were asked to consider the current status of the effectiveness of self‐treatment of TD according to the region into which people travel and the different enteric pathogens likely encountered. PubMed was reviewed for papers on TD treatment, which was augmented by the extensive files maintained on the topic by the authors. The authors provide a perspective on current recommendations for self‐therapy of TD. Outcome measures and future studies needed are presented. A separate Expert Review of the Evidence Base for Prevention of TD has been developed by the authors of this report. Chemoprophylaxis as a means of dealing with TD is discussed in that review. Details of the review process including selection of literature considered by the panel and plans for periodic updating of the evidence base can be found at; click on “ISTM Committees,” and then “Publications.”

Etiologic agents of TD and Their antimicrobial susceptibility as a background

The most important causes of TD are bacterial in origin with two types of diarrhea‐producing Escherichia coli[enterotoxigenic E coli(ETEC) and enteroaggregative E coli(EAEC)] associated with approximately half of the illness in Latin America and Africa. 1–3 In Asia, ETEC and EAEC cause approximately one third of the illness, with infection by the invasive pathogens,Shigella,Salmonella, and Campylobacter seen in up to 20% of the cases. 3–5 There has been a progressive increase in antimicrobial resistance among major bacterial enteric pathogens associated with TD worldwide. Noroviruses cause between 10% to 20% of TD cases, 6 often resulting in vomiting as well as diarrhea. Protozoal parasites are unusual causes of TD but should be considered in anyone with persistent diarrhea (illness lasting ≥14 days) or when antibacterial therapy fails to shorten illness. 7

Chemotherapy, drugs to consider, clinical trials, and concerns

Management of diarrhea includes receipt of electrolytes and calories, symptomatic treatment, and antimicrobial therapy. The panel considered each of the management modalities.

Fluid and Electrolyte Therapy and Diet During TD

Oral rehydration treatment (ORT) has been lifesaving in infants with dehydrating forms of acute diarrhea 8–10 in developing regions and in all age groups with cholera‐like illnesses. 11 TD in older children and otherwise healthy adults is not a life‐threatening condition. Adults with TD or parents of older children are for the most part educated people who know the importance of maintaining fluid intake during episodes of diarrhea. One randomized study of ORT plus loperamide versus loperamide alone was carried out in young adults with TD. 12 The study failed to show clinical improvement or improvement in urine specific gravity in the group receiving ORT treatment when the two groups were compared providing evidence that adults can easily maintain fluid balance by consuming available foods and beverages. During a bout of acute TD, consumption of small quantities of easily digestible foods are recommended to aid in mucosal recovery from enteric infection 13 as has been established in pediatric studies. One study demonstrated that for adults with TD, dietary restrictions afforded no clinical benefit compared with an unrestricted diet. 14 Breast‐fed infants should continue their feedings during and after rehydration, and formula‐fed infants should continue their usual formula immediately upon rehydration in amounts sufficient to satisfy energy and nutrient requirements. Lactose‐free or lactose‐reduced formulas usually are not necessary. A meta‐analysis of clinical trials indicated no advantages of lactose‐free formulas over lactose‐containing formulas for the majority of infants, although some infants with malnutrition or severe dehydration recovered more quickly when given lactose‐free formula. 15 Children receiving semisolid foods or solid foods should continue to receive their usual diet during episodes of diarrhea. 8

Drugs used to relieve symptoms

Nonspecific drugs control symptoms more rapidly than antibacterial drugs but may not cure illness. 16–18 These drugs have value in controlling symptoms of milder forms of TD. For more severe or intense TD, symptomatic drugs, if used, should be combined with antibacterial therapy. The agent that has been evaluated most commonly for symptom relief of TD has been loperamide.

Other symptomatic antidiarrheal drugs have been evaluated including antisecretory agents, which may work through a physiologic mechanism. The first antisecretory drug used was BSS, with antidiarrheal effects working through its salicylate moiety. 19 Acetyl salicylic acid (aspirin) appears to have similar antisecretory effects and has been found to reduce pediatric diarrhea, 20 but acetyl salicylate is toxic to the stomach causing gastric erosions and bleeding 21 not seen with BSS that has gastroprotective effects. 22 Loperamide has antisecretory effects as well as antimotility effects. 23

One antisecretory agent evaluated in TD is zaldaride maleate, an inhibitor of intestinal calmodulin that alters intracellular calcium and transport processes. 24 A second antisecretory drug, crofelemer, blocks intestinal chloride channels and has been used with success in the treatment of TD. 25 A third antisecretory drug, racecadotril, an enkephalinase inhibitor of endogenous opiates, has been used successfully in children 26 and adults 27 with diarrhea but has not been evaluated in TD. Efficacy of the antisecretory drugs with widely varying mechanisms of action shows the complexity of the secretory processes in acute diarrhea. The new antisecretory drugs are in development and not available in most regions of the world.

Antibacterial drugs

Shortly after ETEC was implicated as an important causative agent of TD, 28–30 a study demonstrated the value of antibacterial therapy in shortening the illness. 31 Since then a number of studies have been conducted to establish the value of antibacterial drugs in TD in essentially all areas of the developing world where high rates of diarrhea exist among international travelers (Table 2).

View this table:
Table 2

Double‐blind, placebo‐controlled antibacterial treatment trials in adults with travelers’ diarrhea (including p values)

Duration post‐treatment diarrhea (TLUS) HrsTreatment failures (%)*
Year (location), study drug, and duration, referencePlaceboStudy drugPlaceboStudy drug
1981 (Mexico) TMP/SMX for 5 d 31 9329 (p< 0.001)475 (p< 0.001)
1984 (Mexico) TMP/SMX and Ciprofloxacin (cipro) for 5 d 102 8120 (TMP) and 29 (cipro) (p< 0.001 for both)325 (TMP) and 7 (cipro) (p< 0.0001 for both)
1986–1988 (Mexico) Ofloxacin 5 (of 5 d) and 3 (of 3 d) 103 5639 (of 5) (p= NS) and 28 (of 3) (p< 0.05)2911 (of 5) and 5 (of 3) (p= 0.0001 groups combined)
1993 (Belize) Ciprofloxacin, single dose 33 5425 (p< 0.0001)Not reportedNot reported
1987–1989 (Mexico) TMP/SMX, single dose (SD)and 3 d 80 5928 (SD) (p≤ 0.005) and 34 (3d) (p= NS)5610 (SD) and 9 (3d) (p< 0.05 for both)
1986–1988 (Africa, Asia, Latin America), norfloxacin 104 Not reportedNot reported6226 (p= 0.0001)
1989 (Morocco) norfloxacin, 3 d 105 7929 (p< 0.001)5316 (p< 0.001)
1999–2000 (Guatemala, Mexico, and Kenya), rifaximin for 3 d 93 60600 mg/d 33 and 1,200 mg/d 33 (p= 0.0001 for both)35600 mg/d 16 and 1,200 mg/d 17 (p= 0.001 for both)
2002–2003 (Mexico, Guatemala and India), rifaximin (rif) versus ciprofloxacin 4 66rif 32 (p= 0.0014) and cipro 29 (p= 0.0003)26rif 11 (p= 0.0039) and cipro 17 (p= 0.05)
  • TLUS = time to last unformed stool, calculated from time of initiation of therapy until passage of the last unformed stool after wellness is declared; TMP = trimethoprim; SMX = sulfamethoxazole.

  • * Diarrhea continuing when the study was completed at 5 days (>120 hours).

  • Drugs developed for use in travelers’ diarrhea.

The principal measurements of response to antibacterial therapy in the various placebo‐controlled clinical trials have been duration of post‐treatment diarrhea, called time to last unformed stool (TLUS); failure to respond to treatment; 32 and number of unformed stools passed during illness. 33 TLUS is calculated as the time from taking the first dose of study medication until passage of the last unformed stool after which subjects are declared well (duration of post‐initiation of therapy diarrhea). Published studies have shown that antibacterial drugs shorten the mean or median TLUS compared with the corresponding placebo response (Table 2). Treatment failure, defined as clinical worsening during therapy or failure to achieve wellness by 5 days, 32 is reduced similarly in adults with TD randomized to receive an antibacterial drug compared with a placebo (Table 2). In one placebo‐controlled treatment trial, subjects receiving a placebo passed an average of 11.4 liquid stools during their illness compared with 5.0 liquid stools in a ciprofloxacin‐treated group (p< 0.0001). 33

The drugs with the most extensive evaluation in treatment of TD are trimethoprim/sulfamethoxazole (TMP/SMX) and the fluoroquinolones (ofloxacin, norfloxacin, and ciprofloxacin). TMP/SMX resistance has become widespread, limiting the value of this combination antibiotic. 34 The fluoroquinolones remain active against a high percentage of the etiologic agents of TD. 34 The poorly absorbed (<0.4%) rifaximin and systemically absorbed azithromycin have been shown to be effective treatments of TD. 5,35 The absorbed antibacterial drugs including the fluoroquinolones and azithromycin have been administered for 3 days or for a single dose with no apparent clinically important difference in efficacy between 3‐day and one‐dose treatment in shortening the duration of TD. In various trials, nonabsorbed rifaximin has been given routinely for 3 days.

Available evidence suggests that bacterial species within a genus (Shigella sonnei vs Shigella flexneri) or presence of different virulence factors among diarrhea‐producing species (ETEC strains varying by toxin type produced or EAEC strains differing by virulence factors present) do not translate into differences in required therapy. Enteric infection by Shigella dysenteriae1 (Shiga bacillus) appears to be an exception that may need 5 days of therapy rather than a single‐dose or 3‐day treatment course, 36, 37 but this organism is a rare cause of TD.

There are four microbe‐specific concerns possibly relevant to empiric antibacterial therapy of TD. First is the concern that certain antibacterial drugs can complicate enteric disease caused by Shiga toxin‐producing E coli(STEC) by increasing the risk of hemolytic uremic syndrome (HUS). Some antibiotics promote the release of Shiga‐toxin, 38 while others do not seem to do so. 39–42 A meta‐analysis did not show an association between antimicrobial therapy use in patients with hemorrhagic colitis due to E coli O157:H7 and subsequent development of HUS. 42 STEC are not common causes of TD, minimizing this concern in travel medicine. Enhancement of HUS by antibacterial treatment of S dysenteriae1 diarrhea seems to be a rare event. 43

A second therapeutic concern is that antibacterial drugs may lead to prolongation or worsening of enteric infection caused by strains of nontyphoid Salmonella(NTS). Antibacterial drugs can influence the duration of carriage of an infecting strain of NTS. An often quoted study of treatment of NTS indicated that carriage of the organism was prolonged by at least 3 weeks secondary to ciprofloxacin therapy. 44 A second clinical study failed to see such prolongation of carriage of NTS when patients were treated with either ciprofloxacin or TMP/SMX. 45 NTS strains usually are not spread from person to person due to inoculum size required. Also the short‐term carriage is of little clinical significance to the affected people. 46 A Cochrane analysis of results of therapy of people with gastroenteritis due to Salmonella showed that therapy may result in increased rate of relapse, increase in risk for a positive culture after 3 weeks, and increase risk for adverse drug reaction with no decrease in length of illness. 47

The third treatment concern is that antibacterial therapy with drugs that deplete colonic flora, seen characteristically with fluoroquinolone administration, 48 may predispose to development of Clostridium difficile colitis after therapy of TD. 49, 50 A recent publication reported four patients with TD who developed C difficile colitis following treatment with ciprofloxacin. 51

The fourth area of concern relates to widespread use of antibacterial drugs in both human and animal populations leading to antibacterial resistance among enteric pathogens 34, 52–56 and for the absorbed antibiotics, extraintestinal bacteria. 57 While fluoroquinolone resistance of ETEC strains causing TD has occurred, 56 the major public health concern is fluoroquinolone resistance among strains of Clostridium jejuni or Shigella. 5, 53, 55, 58–60 Fluoroquinolone resistance by Streptococcus pneumonia is of clinical importance. 57

The consensus of authors of this review is that concerns about antibiotic treatment of Shiga toxin‐producing organisms or nontyphoid Salmonella, possible predisposition to C difficile diarrhea, or contribution to antibiotic resistance development are not sufficient reasons to withhold antimicrobial therapy as treatment for TD.

There are a number of potentially important issues related to selection of antibiotics for travel to high‐risk regions. In a randomized, double‐blind treatment study of TD, rifaximin (400 mg twice a day for 3 days) was of equivalent value in shortening TD compared with ciprofloxacin (500 mg twice a day for 3 days) in adults in Mexico, where diarrheagenic E coli are known to be the most common cause of illness. 35 A second study failed to demonstrate an advantage overall when ciprofloxacin was compared with rifaximin therapy in TD in Mexico, Guatemala, and India, yet a subgroup with invasive illness showed reduced benefit following treatment with rifaximin. 4

Three clinical trials demonstrated that azithromycin was as effective as a fluoroquinolone in the treatment of TD occurring in Thailand or Mexico. 5, 60, 61 Azithromycin has also been shown to be active in the treatment of diarrhea caused by invasive strains of Campylobacter, including fluoroquinolone‐resistant strains 5,34 and Shigella spp., 62 and the drug is active against the noninvasive diarrheagenic E coli. 34

For diarrheagenic E coli, the principal causes of TD worldwide, all three antimicrobial drugs used currently to treat TD are effective.Campylobacter strains occurring in most parts of the world show a high degree of resistance to fluoroquinolones including ciprofloxacin. 5,53,63,64 Rates of resistance to Campylobacter strains were found to be high for rifaximin in one study. 65 Erythromycin resistance of Campylobacter spp. in economically developed countries generally is stable at less than 5%, 66, 67 whereas higher resistance has been reported from some countries including Thailand, 59,68 Nigeria, 69 Spain, 55 Taiwan, 70 and Canada. 71 Strains of Campylobacter spp. that show high‐level resistance to erythromycin also appear to be resistant to azithromycin, 72,73 although azithromycin concentrates in tissues and may be effective treatment even when infecting strains show a moderately high minimal inhibitory concentration to the drug.

For fluoroquinolone‐susceptible Campylobacter and the other invasive bacterial pathogens, fluoroquinolones and azithromycin represent the preferred treatments. Invasive bacterial enteropathogens occur more commonly in South Asia, 3–5 when compared with other high‐risk regions, which has led some travel medicine experts to select azithromycin preferentially for travelers to that region, expressing concern that rifaximin would be less effective against invasive pathogens and ciprofloxacin‐like drugs would be less active against resistant strains of Campylobacter.

One difference between the various anti‐TD antibiotics is the expected rate of adverse events. In all clinical trials, nonabsorbed rifaximin has shown the tolerability profile of the placebo control, suggesting that this preparation would have fewer systemic adverse events than absorbed drugs. The adverse events for absorbed drugs are of low but predictable frequency: fluoroquinolones—insomnia, irritability, and Candida vaginitis and azithromycin—gastrointestinal symptoms. In the United States, a black box warning against tendon rupture has been added for the fluoroquinolone agents.

An unproven benefit of antibacterial chemotherapy of TD is prevention of persistent enteric symptoms and chronic diarrhea. Two studies demonstrated that 10% to 12% of adults with TD will progress to postinfectious irritable bowel syndrome (PI‐IBS). 74, 75 One study indicated that PI‐IBS most commonly developed following enteric infection by inflammatory bacterial pathogens. 76 The same research team provided evidence that PI‐IBS persisted in most cases for at least 6 years after disease onset. 77 A separate study also confirmed common persistence of new onset PI‐IBS for at least 5 years after illness began. 78 When treatment is begun only after developing classic TD (passing ≥3 unformed stools plus one or more signs or symptoms of enteric infection such as abdominal pain or cramps), PI‐IBS was not prevented. 74 It is not known if persistent complications can be prevented by starting antimicrobial therapy earlier in the course of enteric infection, after passage of the first unformed stool or at the first presence of signs or symptoms of enteric infection.

Combination therapy

Loperamide can be administered with antibiotics, where the objective of therapy is to combine rapid improvement in symptoms with the symptomatic treatment with slower onset curative effects of the antibacterial drug 79–81 (Table 3). Not all trials have reported benefit of adding loperamide to antibacterial therapy, 82, 83 but all trials have concluded the combination was safe. The rare occurrence of worsening of the disease when antimotility drugs are used alone to treat invasive disease 84 has not been encountered in any of these studies when effective antibacterial therapy also is used.

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Table 3

Clinical treatment studies where antibacterial drugs were combined with loperamide in the treatment of adults with travelers’ diarrhea

Region studiedAntibacterial drug employedComment on additive effectsReferences
MexicoOfloxacinMajor* 79, 106
ThailandCiprofloxacinMinimal 82
MexicoAzithromycinMajor* 107
MexicoRifaximinMajor* 108
  • * Rapid improvement (shortened time from initiation of treatment until time that the last unformed stool during illness was passed, reduction in diarrhea stool number)

Antimicrobial susceptibility and fecal levels of drug

In vitro susceptibility of bacterial strains is an important predictor of clinical response to antibiotic therapy in bacterial diarrhea. 85 The current antimicrobial breakpoints used to determine susceptibility are based on minimal inhibitory concentration (MIC) of the drug for the organism and expected serum concentration of drug. 86, 87 The available breakpoints are likely to be insensitive for predicting the outcome of treatment of intestinal and urinary tract infections when curative drugs concentrate at very high concentrations in the site of infection. For bacterial diarrhea, gut levels of fluoroquinolones exceed 500 μg/g 88–90 and rifaximin reach levels of 8,000 μg/g 91 after 3 days therapy. Azithromycin therapy leads to high tissue levels of the drug during therapy. 92 Studies are needed to develop new breakpoints for enteric pathogens and drugs used to treat intestinal tract infections based on organism MICs and intestinal and mucosal levels of biologically active drug achieved.

While rifaximin improves clinical illness of uncomplicated TD with similar efficiency as therapy with absorbed antibacterial drugs such as flouroquinolones, studies have shown a lower rate of pathogen eradication from stool with rifaximin. 4, 35, 93 The importance of this observation is called into question by results of a previous study showing a lack of correlation between pathogen eradication and clinical improvement of antibacterial therapy of TD. 94 There are at least two possible explanations for variable rates of pathogen eradication in the face of clinical response as occurs with rifaximin. First, bile‐soluble rifaximin may primarily exert its beneficial effect in the bile‐rich small bowel as opposed to the aqueous environment in the colon. Second, the drug may alter pathogen virulence even in subinhibitory concentrations. 95

Specific recommendations for self‐treatment of TD are provided. The strength of each recommendation and the quality of the evidence backing the recommendation are indicated by a rating scale provided inTable 1.

Treatment of TD in children

For children, the mainstay of treatment of TD while in developing regions is fluid and electrolyte therapy and dietary management. TD therapy should center on oral fluid and electrolyte treatment using only bottled or previously boiled water. Breast‐fed infants should continue nursing on demand before, during, and after diarrhea to minimize exposure to contaminated food and beverages and to provide protective factors. 8, 96 Unless it occurs under the direction of a physician, antibacterial and symptomatic therapy should not be used for infants (≤12 months of age).

Therapy with BSS is not recommended for young children because of the concern of excessive salicylate absorption. 97 Loperamide is not recommended due to lack of known efficacy and concern for side effects. Fluoroquinolone treatment currently is not recommended for therapy of TD in children due to potential drug toxicity. 98 Fluoroquinolones while not approved for use in children may be safe for TD therapy since the drugs are given for only 1 to 3 days. 99 Azithromycin is an approved drug in pediatrics and can be given to children with more severe cases of TD in a dose of 10 mg/kg/d for 3 days for children 6 months to 12 years of age. 100 Rifaximin, while not approved for use in children in most countries, should be safe to administer based on weight of the child. Rifaximin is available in a small number of countries as a pediatric suspension.

Current Recommendations and Summary Views on Self‐Treatment of TD

The following statements provide the authors’ perspective on the self‐treatment of TD based on the previous studies outlined above. The recommendations help identify medication to add to the travel kit before leaving home, which may be influenced by the trip destination. The strength and quality of evidence of various treatment options are presented inTable 4.

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Table 4

Clinical evidence for efficacy of the various therapeutic approaches in the management of adults with TD

Therapeutic agentStrength of evidenceQuality of evidenceComments
Bismuth subsalicylateAIInexpensive; will turn stools and tongues black (harmless bismuth sulfide); leads to important salicylate absorption, 97 must take multiple doses; not to be used in persons with advanced acquired immunodeficiency syndrome or with chronic enteric disease where bismuth absorption may occur across the damaged mucosa 109
Kaolin, pectin, or attipulgiteCIClinical trials have shown that these agents make stools more formed without providing other advantages 110
LoperamideAILoperamide is the most effective symptomatically acting antidiarrheal compound 18
Diphenoxylate hydrochloride with atropine (Lomotil)AIEffective but contains atropine which causes anticholinergic side effects without antidiarrheal effects 111 and with overdose liability for children due to central opiate effects 112
TMP/SMXDIIIExpected worldwide resistance limits value of this drug 34
Fluoroquinolones*AIEffective, side effects and concern about stimulation of resistance among extraintestinal bacteria 57
RifaximinAISafest available drug for noninvasive forms of TD due to diarrheagenic E coli strains; not effective for febrile and dysenteric TD
AzithromycinAIEffective against all bacterial forms of TD with its major use being for febrile and dysenteric TD 5
  • TMP = trimethoprim; SMX = sulfamethoxazole; TD = travelers’ diarrhea.

  • * ciprofloxacin, norfloxacin, levofloxacin, ofloxacin.

  1. TD is a nonfatal, self‐limiting illness. Treatment is designed to reduce symptoms and shorten illness limiting the duration of inconvenience, particularly when travelers need to follow a schedule.

  2. Oral fluid and electrolyte requirements in TD can be met in nearly all cases by increasing fluids and salt‐containing foods in the diet. While restriction of diet during diarrhea treatment appears to have no overt clinical benefit, it should be useful for people with acute diarrhea to consume easily digestible foods, which have been demonstrated in children with acute enteric infection to help repair and regenerate enterocytes after intestinal injury.

  3. For most adults with moderate to severe TD without fever or dysentery (passage of bloody stools), one of the three oral treatments listed in alphabetical order may be given and expected to be of equivalent value in shortening illness: (1) azithromycin in a single 1,000 mg dose; (2) fluoroquinolone (ciprofloxacin 750 mg, levofloxacin 500 mg, or norfloxacin 400 mg) given once; with an incomplete response to single dose, the same drug and same dosage can be repeated the next two mornings (3 days therapy); or (3) rifaximin 200 mg three times a day for 3 days.

Some panel members recommend either ciprofloxacin or rifaximin as the standard self‐treatment for travel to Latin America, Africa, and large parts of Asia, reserving azithromycin for all future travelers to South East Asia (mainly Thailand). Others recommend a fluoroquinolone or rifaximin as standard treatment of all nonfebrile, nondysenteric TD regardless of region, including South Asia, reserving azithromycin for treatment failures. Rifaximin is not available in many countries, limiting this choice for many.

  1. When high fever is present (39.4°C) or travelers are passing grossly bloody stools (dysentery), 1,000 mg of azithromycin in a single dose is the recommended therapy for adults. The pediatric dose is 5 mg/kg/d for 3 days. If azithromycin is not selected for standard therapy, travelers may be advised to take two medications with them, either a fluoroquinolone or a rifaximin for uncomplicated illness and azithromycin for febrile or dysenteric illness or when TD fails to respond to primary treatment. Transporting two TD therapies may be confusing for some travelers.

  2. If available, loperamide can be given with one of the antibacterial drugs described above to accelerate recovery and control diarrhea. It is given to adults with diarrhea in a dose of 4 mg initially followed by 2 mg (one capsule) after each unformed stool passed, not to exceed 8 mg (4 capsules) in 24 hours with the total treatment duration ≤48 hours.

  3. An unknown percentage of European travel medicine experts recommend loperamide alone as standard self‐treatment of TD. The dose of loperamide for adults is given above.

Performance, outcome measures, and future research

The following outcome measures will be important to examine as studies of TD therapy are evaluated, and future studies are designed:

  1. The frequency of possession and use of symptomatic and antibacterial therapy in travelers to high‐risk tropical and semitropical regions.

  2. The clinical response to treatment among people with TD by therapeutic agent and geographic area visited.

  3. The frequency of treatment failures and causes of illness in refractory cases.

  4. The antibacterial susceptibility of bacterial enteropathogens recovered from subjects with TD by year of study and geographic location of the illness.

  5. The effectiveness of early initiation of therapy in preventing chronic functional disease of the intestine including PI‐IBS.

  6. The safety and effectiveness of antibacterial drugs for treatment and prevention of TD in children and other special groups including the elderly, the chronically ill or immunosuppressed and the pregnant.

  7. The safety and effectiveness of the newer antisecretory drugs for treatment of TD.

  8. The value of rifaximin treatment of TD in areas where prevalent invasive pathogens are encountered including many areas of Asia.

  9. The occurrence of resistance of each of the important drugs in TD therapy: fluoroquinolones, rifaximin, and azithromycin.

  10. The additive or synergistic value of combining antisecretory drugs with antimicrobial drugs in the treatment of TD.


TD will continue to be a problem of international travel. People traveling to high‐risk regions of the developing world will need to be encouraged to take with them medication for self‐therapy that is known to be effective in controlling symptoms and duration of most cases of TD. Novel antisecretory drugs should be developed for use in therapy of TD with or without concomitant antibacterial treatment in view of the more physiologic approach of these classes of drugs.

Declaration of interests

H.L.D.P has consulted with, received honoraria for speaking and has received research grants administered through his university from Salix Pharmaceutical Company; has received a consulting fee from Romark Institute for Medical Research; has received research grants administered through his university from Optimer Pharmaceuticals and IOMAI Corporation; and has received an honorarium for consulting and/or speaking with McNeil Consumer Healthcare and Merck Vaccine Division.

C.D.E has received speaking honoraria from and is on an advisory board for Salix.

S.G. is a part‐time employee of a pharmaceutical company (Optimer Pharmaceuticals, Inc., San Diego, CA, USA) that is currently in a phase 3 trial to test a drug to treat TD.

L.R. gave lectures and participated in advisory boards and phases II‐II studies SBL vaccine, Sanofi Pasteur MSD, and Glaxo Smith Kline.

R.S. has accepted fee for speaking, organizing and chairing education, consulting and/or serving on advisory boards, also reimbursement for attending meetings and funds for research from Astral, Baxter, Berna Biotech/Crucell, GlaxoSmithKline, Novartis Vaccine, Optimer, Roche, Salix, Sanofi Pasteur MSD, and/or SBL Vaccine.

T.W. receives fee for speaking from Sanofi Pasteur, GSK, UCB, and Novartis Vaccines.

M.J.G.F. and L.K.P. state that they have no conflicts of interest.


  • Guest Editor:Heikki Peltola


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