Perspectives: Antibiotics in Travelers' Diarrhea - Balancing Benefit & Risk

CDC Yellow Book 2024

Preparing International Travelers

Author(s): Mark Riddle, Bradley Connor

Benefit

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 1–2 days, and if the traveler combines an antibiotic with an antimotility agent (e.g., loperamide), duration of illness is shortened even further. Emerging data on the potential long-term health consequences of TD (e.g., chronic constipation, dyspepsia, irritable bowel syndrome) might suggest a benefit of early antibiotic therapy given the association between more severe and longer disease and risk for postinfectious consequences.

Risk

Antibiotics commonly used to treat TD have side effects, some of which are severe but rare. Perhaps of greater concern is the recent understanding that antibiotics used by travelers can contribute to changes in the host microbiome and to the acquisition of multidrug-resistant bacteria. Multiple observational studies have found that travelers (in particular, travelers to South and Southeast Asia) who develop TD and take antibiotics are at risk for colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE).

The direct effect of colonization on the average traveler appears limited; carriage is most often transient, but it does persist in a small percentage of colonized persons. Elderly travelers (because of the serious consequences of bloodstream infections in this population) and those with a history of recurrent urinary tract infections (because Escherichia coli is a common cause) might be at an increased risk for health consequences from ESBL-PE colonization. At a minimum, clinicians should make these travelers aware of the risk and counsel them to convey their travel exposure history to their treating providers if they become ill after travel. Of broader importance, international travel has been associated with subsequent ESBL-PE colonization among close-living contacts, suggesting potentially wider public health consequences from ESBL-PE acquisition during travel.

The Challenge

The challenge providers and travelers face is how to balance the health benefit of short-course antibiotic treatment of TD with the risk for colonization and global spread of resistance. The role played by travelers in the translocation of infectious disease and resistance cannot be ignored, but the ecology of ESBL-PE infections is complex and includes diet, environment, immigration, and local nosocomial transmission dynamics. ESBL-PE infections are an emerging health threat, and addressing this complex problem will require multiple strategies, including antibiotic stewardship.

An Approach

Health care providers need to have conversations with travelers about the multilevel (individual, community, global) and multifactorial risks of developing TD: travel, individual behaviors (e.g., hand hygiene), diet (e.g., safe selection of foods and beverages), and other risk avoidance measures. But then, knowing it is often difficult to prevent or even reduce the risk for TD through behaviors and diet alone, what is the most reasonable way to prepare travelers for empiric TD self-treatment before a trip? Clinicians can strongly emphasize reserving antibiotics for moderate to severe TD and using antimotility agents for self-treatment of mild TD.

When it comes to managing TD, we expect the traveler to be both diagnostician and health care provider. For even the most astute traveler, making an appropriately informed decision about their own health can be challenged by the anxiety-provoking onset of that first abdominal cramp in sometimes austere and inconvenient settings. Given that TD counseling is competing with numerous other pretravel health topics that need to be covered, travel medicine providers might want to develop and implement simple messaging, handouts, or easy-to-access electronic health guidance. Providing travelers with clear written guidance about TD prevention and step-by-step instructions about how and when to use medications for TD is crucial.

Though further studies are needed (and many are under way), a rational approach involves using a single-dose regimen of an antibiotic that minimizes microbiome disruption and risk for colonization. Additionally, as travel and untreated TD independently increase the risk for ESBL-PE colonization, nonantibiotic chemoprophylactic strategies (e.g., self-treatment with bismuth subsalicylate), can 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.

 

The following authors contributed to the previous version of this chapter: Mark S. Riddle, Bradley A. Connor

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;17(1):78–85.

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;24 (Suppl 1):S57–74.

 

. . . perspectives chapters supplement the clinical guidance in this book with additional content, context, and expert opinion. The views expressed do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).