Perspectives: Antibiotics in Travelers’ Diarrhea—Balancing the Risks & Benefits

For the past 30 years, randomized controlled trials have consistently and clearly demonstrated that antibiotics shorten the duration of illness and alleviate the disability associated with travelers’ diarrhea (TD). Treatment with an effective antibiotic shortens the average duration of a TD episode by about a day, and if the traveler combines an antibiotic with an antimotility agent such as loperamide, the duration of illness is shortened even further. Emerging data on the potential long-term health consequences of TD, such as irritable bowel syndrome, dyspepsia, and chronic constipation, might suggest a benefit of early antibiotic therapy given the association between more severe and longer disease and risk of postinfectious consequences.

Although these clinical results are impressive, antibiotics, like any drug, are not without consequences. Each of the antibiotics commonly used to treat TD have side effects, but these are generally mild and self-limiting, and the benefits appear to outweigh the risks. More recently, however, there has been concern that antibiotics used by travelers might result in significant changes in the host microbiome as well as the acquisition of multidrug-resistant bacteria. Multiple observational studies have found that those people who travel (in particular to regions of Asia), develop TD, and take antibiotics are at incrementally increasing risk for colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE). The direct effects of colonization on the average traveler appears limited; carriage is most often transient but does persist in a small percentage of those who are colonized. However, international travel by a household member is associated with ESBL-PE colonization among close-living contacts, which suggests potential larger public health consequences from acquiring ESBL-PE during travel.

The challenge that we face as providers and travelers is how to balance the risk of colonization and the global spread of resistance with the health benefits of antibiotic treatment of TD. Although the role of travelers in the translocation of infectious disease and resistance cannot be ignored, the ecology of ESBL-PE infections is complex and includes environmental, diet, immigration, and local nosocomial transmission dynamics. ESBL-PE infections are an emerging health threat, and addressing this complex problem will require multiple strategies.

How, then, to prepare a traveler with a prescription for empiric self-treatment before a trip? There needs to be a conversation with the traveler about the multilevel (individual, community, global) risks of travel, travelers’ diarrhea, preventing TD through hand hygiene and careful selection of foods and beverages, and antibiotic treatment. Reserving antibiotics for moderate to severe TD should be emphasized strongly, and using antimotility agents alone may be suggested for mild TD. Elderly travelers (because of the serious consequences of bloodstream infections in this population) or those with recurrent urinary tract infections (because Escherichia coli is a common cause) may be at higher risk of health consequences as a result of ESBL-PE colonization. At a minimum these travelers should be made aware of this risk, and should be counseled to convey their travel exposure history to their treating providers if they become ill after travel. Though further studies are needed (and many are underway), a rational approach is advised to decrease exposure by using single-dose regimens and selecting an antibiotic agent that minimizes microbiome disruption and risk of colonization. Additionally, as travel and untreated TD independently increase the risk of ESBL-PE colonization, nonantibiotic chemoprophylactic strategies, such as the use of bismuth subsalicylate, may decrease both the acute and posttravel risk concerns. Strengthening the resilience of the host microbiota to prevent infection and unwanted colonization, as with the use of prebiotics or probiotics, are promising potential strategies but need further investigation.

Finally, we must be cognizant of the fact that we expect the traveler to be the diagnostician, practitioner, and patient when it comes to managing TD. For even the most astute traveler, making such learned decisions can be challenged by the anxiety-provoking onset of that first abdominal cramp in sometimes austere and inconvenient settings. Providing prospective travelers with clear written guidance about TD prevention and step-by-step instructions about how and when to use medications for TD is crucial.

Bibliography

  1. Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A, et al. Import and spread of extended-spectrum β-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study. Lancet Infect Dis. 2017 Jan;17(1):78–85.  [PMID:27751772]
  2. 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 Apr 1;24(Suppl 1):S57–S74.

Authors

Mark S. Riddle, Bradley A. Connor

Notes

Perspectives sections are written as editorial discussions aiming to add depth and clinical perspective to the official recommendations contained in the book. The views and opinions expressed in this section are those of the author and do not necessarily represent the official position of CDC.