Abstract
The use of preventive measures and self-treatment for travelers' diarrhea is routine in regions where the occurrence of diarrhea is predictably high. People traveling to these areas who do not exercise care in their selection of consumed foods and beverages will suffer high rates of illness. Such diarrhea normally affects the traveler for a day, although it can result in chronic postinfectious irritable bowel syndrome. Although systemic antibacterial drugs are effective in preventing diarrhea, their use is not routinely recommended because of side effects and their importance as a therapy for extra-intestinal infections. This review focuses on current and future uses of antibacterial drugs in the prevention and therapy of travelers' diarrhea. Minimally absorbed (<0.4%) rifaximin can effectively reduce the occurrence of travelers' diarrhea without side effects. Bismuth subsalicylate is a useful alternative, although it is less effective than rifaximin for the prevention of travelers' diarrhea and the required doses are less convenient. All people who travel to high-risk areas should take curative antimicrobial agents with them for self-treatment of illness: rifaximin 200 mg three times a day for 3 days, or an absorbable agent such as a fluoroquinolone or azithromycin taken in a single dose initially, with the need for a second or third dose determined by clinical response. Loperamide (up to 8 mg per day for ≤2 days) can be given with the antibiotic to offer rapid symptomatic improvement. In the future, the ability to evaluate the genetic risk of illness acquisition might allow person-specific recommendations to be made.
Similar content being viewed by others
Introduction
Approximately 20 million episodes of diarrhea occur annually in people traveling from industrialized regions to developing countries. The world can be divided into three regions depending upon the risk of acquiring travelers' diarrhea for visitors from industrialized and low-risk regions (Figure 1).
The success of antibacterial chemoprophylaxis in treating diarrhea provided the first evidence that bacteria are responsible for most episodes of the illness.1 Studies demonstrating that antibacterial drugs were effective in the treatment of travelers' diarrhea were first carried out in 1980 and 1981, with each study published 2 years later.2,3
Thanks to microbiology studies4 and the response of patients to antibacterial treatment, we now know that about 80% of cases of travelers' diarrhea are due to bacterial agents. There are three main causes of diarrhea. Diarrheogenic Escherichia coli, including enterotoxigenic E. coli and enteroaggregative E. coli, is responsible for ∼50% of cases. The invasive bacterial pathogens Campylobacter jejuni, Shigella, Salmonella and invasive E. coli cause ∼10–25% of cases, with the highest frequencies in southern Asia.4,5 In ∼20% of cases no pathogen is detectable; because they seem to be both treated and prevented by antibacterial drugs,3,7,8,9 most of these cases are caused by undefined bacterial pathogens.6 In coastal areas of the world, non-cholera Vibrio species cause a small percentage of diarrhea. V. cholerae can cause travelers' diarrhea in epidemic areas but cholera is rare in international travelers.
Regardless of cause, most cases of travelers' diarrhea have a similar clinical appearance, with patients complaining of watery diarrhea with abdominal pain or cramps of variable severity. Fever and dysentery (gross blood in stool) are infrequent and are documented in 1–3% of cases.10,11,12 Illness generally incapacitates the traveler for about 1 day.13 Diarrhea persists for more than 2 weeks in ∼2–10% of cases14 and as many as 10% of patients develop what is now recognized as POSTINFECTIOUS IRRITABLE BOWEL SYNDROME (IBS).15 With postinfectious IBS, chronic gastrointestinal complaints occur with abdominal discomfort or pain that can be relieved by defecation and/or a change in bowel pattern and stool form (intermittent diarrhea and constipation), bloating, abdominal distention, passage of mucus, fecal straining, urgency or feeling of incomplete evacuation.
Prevention of illness
The objectives of disease prevention are to eliminate the incapacitation that is associated with diarrhea and the possibility of chronic enteric complications post-diarrhea. Success in these areas will help reduce the fear of acquiring diarrhea, which can often lead to failed travel plans, preventing business development with economic implications for all concerned.
Food and beverage selection
More research is needed to determine how to motivate travelers to select safer food and beverage items, which would reduce the rates of developing diarrhea.16 The frequently safe foods include those served steaming hot (≥59 °C), dry items such as bread, those with high sugar content such as syrups, jellies and honey, and fruit that can be peeled. The often unsafe foods include moist foods served at near room temperature.
Chemoprevention
A study carried out in 1957 that was published in 1959 showed that 35% of US travelers regularly took preventive drugs during visits to Mexico and that this was the recommended approach at the time.1 Although there are no recent studies of the use of prophylaxis because of current travel medicine recommendations,17 antimicrobial chemoprophylaxis appears to be less common.
In studies carried out during the 1980s and 1990s, bismuth subsalicylate, PROBIOTICS and a variety of antibiotics were tried as a means of reducing the occurrence of enteric illness during travel to high-risk areas. These potentially useful agents are listed in Table 1. In Table 1, the expected number of travelers projected to experience diarrhea while in high-risk locations and taking a particular drug is given based on an identified protection rate that assumes a 40% diarrhea rate in those without chemoprophylaxis.18,19
Bismuth subsalicylate
Bismuth subsalicylate has antibacterial properties and prevents 65% of expected travelers' diarrhea cases when a total dose of 2.1 g per day is taken as four equally divided doses at meals and at bedtime.19 Bismuth subsalicylate causes harmless darkening of the tongue and stools and, on direct questioning, tinnitus in a small number of treated subjects. Compliance with this preventive approach is always a concern.
Probiotics
The use of probiotics, living bacterial cultures that inhibit potential colonizing bacteria, has been evaluated for the prevention of travelers' diarrhea. In a group of travelers to various international destinations, the probiotic Lactobacillus GG prevented travelers' diarrhea in 47% of those who would have been expected to develop the condition.20 Although the use of Lactobacillus GG or other probiotics is not currently recommended because of their low efficacies, the search for new and more effective probiotics is warranted in view of the intrinsic safety of these agents.
Antimicrobial drugs
When enterotoxigenic E. coli was established as the main cause of travelers' diarrhea,21 antimicrobial agents were tested as preventive drugs. Despite well-documented concerns about the photosensitivity of treated patients, DOXYCYCLINE was successfully employed as a preventive therapy more than two decades ago.22 Because of current high levels of doxycycline resistance among enteric bacterial pathogens worldwide, this antibacterial drug is currently not recommended for the prevention of travelers' diarrhea. During the 1980s, before resistance to the drug became widespread, TRIMETHOPRIM-SULFAMETHOXAZOLE was found to be effective in preventing travelers' diarrhea.23 Despite an increase in bacterial resistance to many drugs,24 the FLUOROQUINOLONES have been shown to prevent most cases of travelers' diarrhea.7,25,26,27
In 1985, an NIH Consensus Statement concluded that antibacterial chemoprophylaxis with absorbed drugs, such as trimethoprim-sulfamethoxazole or the fluoroquinolones, should not be routinely used because of the possible side effects and the potential for stimulating bacterial resistance to agents needed for the treatment of extraintestinal infections.28 Recommendations for the treatment of breakthrough diarrhea that might occur during fluoroquinolone prophylaxis, however, are unclear when the drug failing to prevent the initial diarrhea, presumably owing to a resistant microorganism, is also one of the recommended treatments. Seven years later in a meeting of specialists from Europe and the US it was concluded that use of prophylaxis with absorbed drugs should be considered (in spite of the possible side effects) for travelers to high-risk areas who would not adhere to strict guidelines for avoiding potentially contaminated food and drink (see above).29 Although prophylaxis with absorbed drugs is not recommended for all travelers, this approach was felt by the group reviewing guidelines to be useful for people performing high-risk travel who also had higher risk of infection, such as those with advanced AIDS, the elderly, or in the presence of an unstable medical problem such as insulin-dependent diabetes, cancer or liver disease.18
When studies demonstrated the value of nonabsorbed drugs for the treatment or prevention of travelers' diarrhea,2,9,30 a minimally absorbed (<0.4%) rifamycin-derivative being used in Italy, rifaximin, was evaluated. Rifaximin successfully prevented travelers' diarrhea in a placebo-controlled trial among more than 200 US college students during their first 2 weeks in Mexico, with diarrhea occurring in 15% of students taking rifaximin and 54% taking a placebo, which gives the drug a protection rate of 72–77%.31 Rifaximin 200 mg was equally effective when taken with meals once, twice or three times a day. Rifaximin was shown in this study and others to be free of detectable side effects, with minimal alteration of colonic flora.
A study to determine the effect of rifaximin in the prevention of diarrhea due to invasive pathogens is being planned for international travelers to Asia. As volunteers given rifaximin prophylaxis are protected against experimental Shigella challenge, rifaximin is likely to reduce the occurrence of invasive disease.32 My research group is also planning a study to evaluate prophylactic rifaximin in the prevention of postinfectious IBS. If chemoprophylaxis with rifaximin successfully prevents diarrhea from invasive pathogens and postinfectious IBS, recommendations for rifaximin chemoprophylaxis in international travelers should become routine.
Prophylaxis is a cost-effective way of reducing the occurrence of diarrhea.33 Use of a safe and effective poorly absorbed antimicrobial (such as rifaximin) is preferable because it will not cause systemic side effects and should not encourage the development of resistance in pathogenic bacteria outside the gut. This should encourage more liberal use of chemoprophylaxis in preventing illness among international travelers.
Options for treatment
Fluids, diet and symptomatic treatment
When otherwise healthy travelers develop diarrhea they should be encouraged to consume fluids and salty foods. Oral fluid treatment that is more active should be considered for very young or old travelers or for those with profuse cholera-like diarrhea. Antisecretory and antimotility drugs decrease the number of stools passed by patients with travelers' diarrhea but do not shorten the duration of illness. The ingestion of food while ill is recommended to facilitate enterocyte renewal and speed up recovery.34
Antimicrobial therapy
Showing the in vitro activity of antibacterial drugs against the likely causative bacteria of travelers' diarrhea is of use in predicting the value of the drug in shortening the duration of illness. The primary efficacy parameter in clinical trials evaluating antimicrobial agents for treatment is the time from initiation of therapy until the last unformed stool is passed (TLUS); wellness is declared at this point.35 Antibacterial drugs with in vitro activity have been shown to reduce TLUS in cases of travelers' diarrhea by 1–3 days compared with no therapy or placebo (Table 2). A second clinical parameter in the evaluation of therapy is treatment failure or failure to achieve wellness after 5 days of observation. Active antibacterial drugs significantly reduce the treatment failure rate from 27–56% for placebo treatment, to 4–17%.18 Some of the illnesses that persist after treatment relate to the presence of nonbacterial or antimicrobial-resistant pathogens, especially Campylobacter.
Use of rifaximin 400 mg twice a day for 3 days and ciprofloxacin 500 mg twice a day for 3 days (the usual recommended dose) is associated with similar rates of TLUS (25.7 h and 25.0 h, respectively) and treatment failure (10% and 6%, respectively).36 In a multicenter, multidose, placebo-controlled study, rifaximin was effective in shortening the duration of diarrhea and in reducing the rate of treatment failure with a similar side-effect profile to placebo.37 The in vitro susceptibility of bacteria to rifaximin is moderately high (16–32 μg/ml)24 but, as rifaximin is minimally absorbed, fecal levels of the drug exceed 8,000 μg/g after 3 days of therapy, far exceeding inhibitory levels.38 Although rifaximin is as effective as the fluoroquinolones for the management of the WATERY DIARRHEA SYNDROME,36 the less common cases of febrile dysentery, usually caused by strains of Shigella or Campylobacter, are best treated with a systemic antibiotic, such as a fluoroquinolone or azithromycin, which is able to reach the organisms that have invaded the intestine. Nonabsorbed drugs are primarily active at the surface of the gut mucosa.
As a result of the widespread use of ciprofloxacin in humans and fluoroquinolone use in animal populations over the past few decades, antibacterial resistance to ciprofloxacin has become a growing problem, particularly among strains of Campylobacter.5,24,39 Unlike the related drug rifampin, rifaximin has a low potential for the development of resistance of colonic flora when used both for prophylaxis40 and therapy.41 This is probably related to the low aqueous colonic solubility of the drug.
As antimicrobial resistance increases with more widespread use of these drugs, newer drugs with less potential for the development of resistance should be sought. Encouragingly, rifaximin resistance is not thought to have emerged after nearly two decades of use in Italy. Rifaximin is currently licensed in 18 countries: Argentina, Bulgaria, China, Colombia, Czech Republic, Greece, Hungary, Italy, Korea, Lebanon, Mexico, Pakistan, Poland, Romania, Spain, Tunisia, United States and Venezuela. A pediatric suspension form is also available in a number of these countries.
The newer fluoroquinolones, gatifloxacin and moxifloxacin, have been shown to have high in vitro activity against enteric pathogens, and have shown greater activity against Campylobacter than ciprofloxacin in both a published study,42 and in an unpublished study of multi-resistant strains in our laboratory (Z-D Jiang and HL DuPont, unpublished data). These drugs offer another advantage in that they can be used by international travelers for the treatment of diarrhea as well as respiratory tract bacterial infections. Table 3 lists the newer drugs with potential value in the therapy and selective prophylaxis of travelers' diarrhea, with comments about their use. A program of monitoring for antibacterial resistance among prevalent bacterial pathogens in high-risk regions should be developed to help identify the drugs for which the least resistance develops.
Empiric therapy recommendations
Everyone who ventures into high-risk regions of the tropical and semi-tropical world should be encouraged to take an antibiotic with them for self-treatment if diarrhea should develop. When to initiate treatment is currently unclear; if treatment is delayed until illness is fully developed, valuable time is lost because it takes nearly a day for antibacterial drugs to cure the illness. On the other hand, if treatment is initiated with the passage of the first unformed stools, people might be exposed to antibiotics unnecessarily, because changes in stool form are not always indicative of illness. The advice given is to allow the traveler to determine when to initiate therapy based on how they feel. Many debilitating enteric illnesses are associated with excessive abdominal complaints including cramps and pain, with minimal degrees of diarrhea.
Loperamide can be given for the treatment of the watery diarrhea syndrome, along with antibacterial therapy for additive effects.43 Loperamide rapidly decreases the passage of diarrhea stools, while antibacterial drugs shorten or cure the enteric infection. There is sufficient concern about Campylobacter and other invasive pathogens that are present in Thailand, and possibly other parts of Southern Asia, to recommend that travelers take an absorbed drug with them in case they develop fever or dysentery with their illness. In these areas, however, watery E. coli-type diarrhea is still frequently encountered and rifaximin is usually appropriate for self-treatment. The absorbable drug can thus be reserved for treatment of nonresponsive illness.
In May 2004, the US FDA approved rifaximin for the treatment of travelers' diarrhea caused by noninvasive strains of diarrheogenic E. coli. In view of the fact that the overall treatment failure rate for absorbable drugs and rifaximin are equivalent (approximately 10%), and because of the prevalence of E. coli forms of diarrhea in international travelers, rifaximin is suitable as a single drug for self-treatment of diarrhea for travelers to destinations outside of Asia. Unless travelers take several drugs with them, it is not possible to provide coverage for all treatable forms of illness with a single drug. Also, all bacterial forms of travelers' diarrhea are self-limiting, which decreases the need for very broad coverage of all potential bacterial and parasitic pathogens.
Future directions for improved treatment strategies
In view of the lack of improvements in food hygiene in developing regions for more than a half a century, and with a current lack of attention to this area, it is unlikely that the risk of acquiring diarrhea in most high-risk areas will be altered in the foreseeable future. Thus, we must continue to educate the public about food and beverage safety and look at effective ways to improve peoples' selection of appropriate foods. As national programs have failed to improve food and beverage quality in most areas, universities or travel medicine organizations could work with industry or local governments to develop definable safe havens through education of hotel and restaurant employees and by monitoring local hygiene and food sanitation: this has occurred successfully in Jamaica.44 At present, all travelers to high-risk areas should be advised of the risk of illness and be armed with antibacterial therapy for self-treatment of resultant illness (see Table 2). Prophylaxis is a cost-effective means of reducing risk of illness for many travelers. Monitoring of antimicrobial susceptibility patterns worldwide will be needed to maintain the best contemporary recommendations for the traveling public. One of the exciting areas of research in this area is the definition of host genetic susceptibility to the bacterial pathogens that cause travelers' diarrhea.45 In the future it might be possible to develop an individual pre-travel strategy through which self-treatment and chemoprophylaxis would be tailored to individual genetic risk makeup.
Conclusions
At present, chemoprophylaxis with minimally absorbed rifaximin is recommended for travelers who are not likely to be careful about dietary restrictions and for those who are concerned about the temporary disability and postinfectious complications of diarrhea. If future studies confirm the high risk of postinfectious IBS in travelers' diarrhea and the effectiveness of chemoprophylaxis in this setting, broader use of preventive rifaximin should be pursued. All travelers to high-risk areas should be armed with antibacterial drugs to treat illness that occurs during international travel. Currently rifaximin 200 mg three times a day for 3 days is the safest treatment and is equally as effective as systemic antibiotics against most cases of travelers' diarrhea. Absorbed drugs are preferred for the less common symptoms of fever and dysentery. With bacterial resistance to ciprofloxacin increasing, one of the newer fluoroquinolones or the azalide, azithromycin, should become the preferred absorbed agent. The fluoroquinolones with broader activity, such as levofloxacin, gatifloxacin and moxifloxacin, offer advantages for a travel medicine kit, because a single agent might be appropriate for therapy of diarrhea, respiratory and bacterial urinary tract infections.
Review criteria
A PubMed search of articles and abstracts published since 1990 was carried out using the terms “traveler's diarrhea”, “travelers' diarrhea”, “traveller's diarrhoea”, and “travellers' diarrhoea”. In addition, articles from a personal library of more than 1,000 publications on the topic from the 1950s until the present time were reviewed.
References
Kean BH, Waters SR (1959) The diarrhea of travelers. III. Drug prophylaxis in Mexico. N Engl J Med 261: 71–74
Ericsson CD et al. (1983) Bicozamycin, a poorly absorbable antibiotic, effectively treats travelers' diarrhea. Ann Intern Med 98: 20–25
DuPont HL et al. (1982) Treatment of travelers' diarrhea with trimethoprim/sulfamethoxazole and with trimethoprim alone. N Engl J Med 307: 841–844
Jiang ZD et al. (2002) Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay). J Infect Dis 185: 497–502
Hoge CW et al. (1998) Trends in antibiotic resistance among diarrheal pathogens isolated in Thailand over 15 years. Clin Infect Dis 26: 341–345
Caeiro JP et al. (1999) Improved detection of enterotoxigenic Escherichia coli among patients with travelers' diarrhea, by use of the polymerase chain reaction technique. J Infect Dis 180: 2053–2055
Scott DA et al. (1990) Norfloxacin for the prophylaxis of travelers' diarrhea in U.S. military personnel. Am J Trop Med Hyg 42: 160–164
DuPont HL et al. (1992) Five versus three days of ofloxacin therapy for traveler's diarrhea: a placebo-controlled study. Antimicrob Agents Chemother 36: 87–91
DuPont HL et al. (1992) Oral aztreonam, a poorly absorbed yet effective therapy for bacterial diarrhea in US travelers to Mexico. JAMA 267: 1932–1935
Mattila L (1994) Clinical features and duration of traveler's diarrhea in relation to its etiology. Clin Infect Dis 19: 728–734
Haberberger RL Jr et al. (1991) Travelers' diarrhea among United States military personnel during joint American-Egyptian armed forces exercises in Cairo, Egypt. Mil Med 156: 27–30
Ericsson CD et al. (1987) Clinical presentation as a guide to therapy for travelers' diarrhea. Am J Med Sci 294: 91–96
von Sonnenburg F et al. (2000) Risk and aetiology of diarrhoea at various tourist destinations. Lancet 356: 133–134
DuPont HL and Capsuto EG (1996) Persistent diarrhea in travelers. Clin Infect Dis 22: 124–128
Okhuysen PC et al. (2004) Post-diarrhea chronic intestinal symptoms and irritable bowel syndrome in North American travelers to Mexico. Am J Gastroenterol 99: 1774–1778
Kozicki M et al. (1985) 'Boil it, cook it, peel it or forget it': does this rule prevent travellers' diarrhoea? Int J Epidemiol 14: 169–172
DuPont HL and Steffen R (Eds; 2001) Textbook of Travel Medicine and Health. Second Edition Hamilton: B.C. Decker, Inc
DuPont HL and Ericsson CD (1993) Prevention and treatment of traveler's diarrhea. N Engl J Med 328: 1821–1827.
DuPont HL et al. (1987) Prevention of travelers' diarrhea by the tablet formulation of bismuth subsalicylate. JAMA 257: 1347–1350
Hilton E et al. (1997) Efficacy of Lactobacillus GG as a Diarrheal Preventive in Travelers. J Travel Med 4: 41–43
Gorbach SL et al. (1975) Travelers' diarrhea and toxigenic Escherichia coli. N Engl J Med 292: 933–936
Sack DA et al. (1978) Prophylactic doxycycline for travelers' diarrhea. Results of a prospective double-blind study of Peace Corps volunteers in Kenya. N Engl J Med 298: 758–763
DuPont HL et al. (1983) Prevention of travelers' diarrhea with trimethoprim-sulfamethoxazole and trimethoprim alone. Gastroenterology 84: 75–80
Gomi H et al. (2001) In vitro antimicrobial susceptibility testing of bacterial enteropathogens causing traveler's diarrhea in four geographic regions. Antimicrob Agents Chemother 45: 212–216
Wistrom J et al. (1987) Norfloxacin versus placebo for prophylaxis against travellers' diarrhoea. J Antimicrob Chemother 20: 563–574
Rademaker CM et al. (1989) Results of a double-blind placebo-controlled study using ciprofloxacin for prevention of travelers' diarrhea. Eur J Clin Microbiol Infect Dis 8: 690–694
Johnson PC et al. (1986) Lack of emergence of resistant fecal flora during successful prophylaxis of traveler's diarrhea with norfloxacin. Antimicrob Agents Chemother 30: 671–674
Gorbach S and Edelman R (Eds; 1986) Travelers' diarrhea: National Institutes of Health Consensus Development Conference Bethesda, Maryland, January 28–30, 1985. Rev Infect Dis 8 (Suppl 2): S109–S233
Farthing MJG et al. (1992) Treatment and prevention of travellers' diarrhoea. Gastroenterology International 5: 162–175
Ericsson CD et al. (1985) Efficacy of bicozamycin in preventing traveler's diarrhea. Gastroenterology 88: 473–477
DuPont H et al.: Randomized placebo controlled trial of rifaximin prevention of travelers' diarrhea in Mexico where diarrheagenic E. coli are major causes of illness. Ann Intern Med, in press
Taylor D et al. (2004) Double-blind, placebo-controlled trial to evaluate the use of rifaximin (200 mg TID) to prevent diarrhea in volunteers challenged with Shigella flexneri 2a (2457T). Amer Soc Trop Med Hyg, Miami, Poster number 2079
Reves RR et al. (1988) A cost-effectiveness comparison of the use of antimicrobial agents for treatment or prophylaxis of travelers' diarrhea. Arch Intern Med 148: 2421–2427
Banwell JG (1986) Treatment of travelers' diarrhea: fluid and dietary management. Rev Infect Dis 8 (Suppl 2): S182–S187
DuPont HL et al. (1992) Evaluation of new anti-infective drugs for the treatment of acute infectious diarrhea. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis 15 (Suppl 1): S228–S235
DuPont HL et al. (2001) Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial. Clin Infect Dis 33: 1807–1815
Steffen R et al. (2003) Therapy of travelers' diarrhea with rifaximin on various continents. Am J Gastroenterol 98: 1073–1078
Jiang ZD et al. (2000) In vitro activity and fecal concentration of rifaximin after oral administration. Antimicrob Agents Chemother 44: 2205–2206
Vila J et al. (2000) Quinolone resistance in enterotoxigenic Escherichia coli causing diarrhea in travelers to India in comparison with other geographical areas. Antimicrob Agents Chemother 44: 1731–1733
DuPont HL et al.: Rifaximin prevention of travelers' diarrhea in Mexico. A randomized placebo controlled trial. Ann Intern Med, in press
DuPont HL and Jiang ZD (2004) Influence of rifaximin treatment on the susceptibility of intestinal Gram-negative flora and enterococci. Clin Microbiol Infect 10: 1009–1011
Krausse R and Ullmann U (2003) In vitro activities of new fluoroquinolones against Campylobacter jejuni and Campylobacter coli isolates obtained from humans in 1980 to 1982 and 1997 to 2001. Antimicrob Agents Chemother 47: 2946–2950
Ericsson CD et al. (2001) Optimal dosing of ofloxacin with loperamide in the treatment of non-dysenteric travelers' diarrhea. J Travel Med 8: 207–209
Ashley DV et al. (2004) Interventions to prevent and control food-borne diseases associated with a reduction in traveler's diarrhea in tourists to Jamaica. J Travel Med 11: 364–367
Jiang ZD et al. (2003) Genetic susceptibility to enteroaggregative Escherichia coli diarrhea: polymorphism in the interleukin-8 promotor region. J Infect Dis 188: 506–511
Ericsson CD et al. (1987) Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial. Ann Intern Med 106: 216–220
Wistrom J et al. (1989) Short-term self-treatment of travellers' diarrhoea with norfloxacin: a placebo-controlled study. J Antimicrob Chemother 23: 905–913
Mattila L et al. (1993) Short-term treatment of traveler's diarrhea with norfloxacin: a double-blind, placebo-controlled study during two seasons. Clin Infect Dis 17: 779–782
Salam I et al. (1994) Randomised trial of single-dose ciprofloxacin for travellers' diarrhoea. Lancet 344: 1537–1539
Adachi JA et al. (2003) Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis 37: 1165–1171
Acknowledgements
The travelers' diarrhea studies by the author that are reported herein have been supported by active grants from, among others, the US Public Health Service, which funds the Texas Gulf Coast Digestive Diseases Center, the National Institutes of Allergy and Infectious Diseases, and the Clinical Research Center, which funds the University of Texas General Clinical Research Center.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The author would like to acknowledge that over the last 30 years he has received a consultant fee, honoraria for speaking and research grants to his institution from various pharmaceutical companies: A.H. Robins Company; Alfa Wassermann SpA; Bristol-Myers Squibb; Burroughs Wellcome Company; Ciba-Geigy Ltd; Hoffmann-LaRoche Inc; Janssen Pharmaceutica; McNeil Consumer Products; Merck Sharp and Dohme; Merrell Dow Pharmaceuticals Inc; Norwich Pharmacal Company and Norwich-Eaton Pharmaceuticals; Ortho Pharmaceuticals; Otsuka Pharmaceuticals; Procter & Gamble Company; Romark Laboratories; Shaman Pharmaceuticals Inc; Salix Pharmaceuticals (the manufacturer of rifaximin); SmithKline Beecham Biologicals; Upjohn Company; and Zyma SA.
Glossary
- POSTINFECTIOUS IRRITABLE BOWEL SYNDROME (IBS)
-
A common, chronic illness causing abdominal bloating with diarrhea and/or constipation following an initial bout of infectious diarrhea
- PROBIOTICS
-
Live bacteria that can be taken orally, potentially providing protection against subsequently ingested pathogens
- DOXYCYCLINE
-
An oral tetracycline antibacterial drug
- TRIMETHOPRIM-SULFAMETHOXAZOLE
-
A combination antimicrobial drug currently not recommended for the treatment of travel diarrhea because of high rates of resistance worldwide
- FLUOROQUINOLONES
-
Considered by many the optimal drugs for therapy and prevention of travelers' diarrhea; antibacterial resistance to ciprofloxacin is, however, high
- WATERY DIARRHEA SYNDROME
-
Liquid stools that are commonly passed by patients with travelers' diarrhea, particularly in cases caused by diarrheogenic E. coli
Rights and permissions
About this article
Cite this article
DuPont, H. Travelers' diarrhea: antimicrobial therapy and chemoprevention. Nat Rev Gastroenterol Hepatol 2, 191–198 (2005). https://doi.org/10.1038/ncpgasthep0142
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ncpgasthep0142
This article is cited by
-
Antibiotic resistance in Campylobacter and other diarrheal pathogens isolated from US military personnel deployed to Thailand in 2002–2004: a case–control study
Tropical Diseases, Travel Medicine and Vaccines (2017)
-
Treatment of Traveler’s Diarrhea
Current Treatment Options in Infectious Diseases (2014)
-
Ashes to ashes
Nature Reviews Gastroenterology & Hepatology (2010)