TD PREVENTION
Emphasize food and beverage precautions
It might be reasonable to expect that travelers who are circumspect about their food and beverage choices on trips will be able to avoid TD. Indeed, this is the basis for the aphorism, “Boil it, peel it, or forget it.” Guidelines routinely recommend that travelers restrict their selection of foods to those that have been well cooked and are served while still very hot, as well as to fruits and vegetables that they peel themselves. Likewise, they should drink only beverages that have been boiled or are in sealed bottles or under carbonation and served without ice.10-12
Many travelers might find these recommendations too restrictive to follow faithfully. Moreover, studies suggest it may not be possible for even the most assiduous traveler to fully avoid the risk for TD.13,14 The hygienic characteristics of the travel destination may be more determinative, as illustrated by the successful reduction of TD rates in Jamaica by improving sanitation in tourist resorts.15
Antibiotic chemoprophylaxis: A debated practice with limited consensus
The etiologic agents of TD are multiple and vary somewhat in predominance according to geographic region.3,16,17 Table 1 depicts variance by region. The most common pathogens are strains of the bacterium Escherichia coli, particularly enterotoxigenic (ETEC), enteroaggregative, and enteropathogenic strains.16 Other bacteria of importance are Campylobacter, Salmonella, and Shigella. Viruses, particularly norovirus (notably connected with cruise ships), can also cause TD, although it is implicated in no more than 17% of cases.18 Parasitic pathogens are even less common causes of TD (4% to 10%) and mainly involve the protozoa, Giardia lamblia, and, to a lesser extent, Entamoeba histolytica and Cryptosporidium.
Although some pathogens often have a characteristic presentation—such as frothy, greasy diarrhea in the case of G lamblia—in general, they cannot be reliably distinguished from one another clinically. Notably, up to 50% of stool samples from TD patients do not yield any pathogen,16 raising the suspicion that current diagnostic technology is not sufficiently sensitive to routinely identify certain bacteria.
There is no consensus on recommending antibiotic chemoprophylaxis against TD.
Opponents of this practice point out that TD is generally a brief (three to five days), self-limited illness.10-12,19,20 Moreover, concerns about antibiotic resistance have come to pass. Previously used agents (trimethoprim-sulfamethoxazole and doxycycline) are no longer effective in preventing or treating TD. In addition, antibiotic use carries the risk for allergic reactions, as well as other adverse effects including (ironically) the development of antibiotic-associated and Clostridium difficile diarrhea.
Proponents of antibiotic chemoprophylaxis point to its demonstrated efficacy in reducing the risk for TD by 4% to 40%.11,21,22 They also argue that at least 20% to 25% of travelers who get TD must significantly curtail their activities for a day or more.1,23 This change in travel plans is associated not only with significant personal loss but also imposes a financial burden.23 Furthermore, TD is known to have longer-term effects. Up to 10% of those affected develop postinfectious irritable bowel syndrome (PI-IBS) that can last for five or six years.21,22,24,25 It is not known, however, whether the use of antibiotic chemoprophylaxis significantly reduces the incidence of PI-IBS.
Finally, the luminal antibiotic rifaximin, nonabsorbable as it is, is very well tolerated and holds promise for not inciting antibiotic resistance.22 However, while its efficacy in preventing TD has been demonstrated in various settings,22,26,27 it is not approved by the FDA for this indication. Also, concerns persist that it might not be effective in preventing TD caused by invasive pathogens.19
Indications on which all agree. Even opponents of antibiotic chemoprophylaxis grant that it is probably warranted for two groups of travelers.10-12 The first is those whose trip schedule is of such importance that any deviation would be intolerable. The second is travelers with comorbidities that would render them at high risk for serious inconvenience or illness if they developed TD. Examples of the latter include patients with enterostomies, mobility impairments, immune suppression, inflammatory bowel disease, and renal or metabolic diseases.
Chemoprophylaxis regimens. If you prescribe an antibiotic prophylactically, consider daily doses of a fluoroquinolone (eg, ciprofloxacin 500 mg orally once daily, not twice daily as for treatment) or rifaximin 200 mg orally once or twice a day, for no longer than two to three weeks.10
Nonantimicrobial chemoprophylaxis
Bismuth subsalicylate has reduced the incidence of TD from 40% to just 14% when taken in doses of two chewable tablets or 60 mL of liquid four times daily.11,19,22 However, the dosing frequency can hinder adherence. Moreover, the relatively high doses required raise the risk for adverse drug reactions, such as blackening of the tongue and stool, nausea, constipation, Reye syndrome (in children younger than 12), and possibly tinnitus. The salicylate component of the drug poses a threat to patients with aspirin allergy or renal disease and those taking anticoagulants. Drug interactions with probenecid and methotrexate are also possible. Bismuth is not recommended for use for longer than three weeks, or for children younger than 3 years or pregnant women in their third trimester.
Probiotics such as Lactobacillus and Saccharomyces are among the other nonantimicrobial chemoprophylaxis agents. These preparations of bacteria and fungi are marketed either singly or in blends of varying composition and proportion. The evidence is divided on their efficacy, and even though some meta-analyses have concluded probiotics such as Saccharomyces boulardii are useful in preventing TD, endorsement in clinical guidelines is muted.10-12,28-30
Immunizations have limited value so far
Natural immunity to E coli gastrointestinal infection among indigenous people in less developed countries has raised the possibility of a role for vaccines in preventing TD. Some strains of ETEC produce a heat-labile toxin (LT) that bears significant resemblance to the toxin produced by Vibrio cholerae. Therefore, the oral cholera vaccine has been marketed outside the United States for the prevention of TD.19,22 However, only ≤ 7% of TD cases worldwide would be prevented by routine use of this vaccine.31 A transdermal LT vaccine, which involves the antigen-presenting Langerhans cells in the superficial skin layers, is promising but not yet available for routine use.19,22
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