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Reply to Connor

  1. David R. Hill1,
  2. Edward T. Ryan2,3,
  3. David O. Freedman4,
  4. Frank J. Bia5,
  5. Philip R. Fischer6,
  6. Jay S. Keystone9,
  7. Phyllis E. Kozarsky7, and
  8. Richard D. Pearson8
  1. 1National Travel Health Network and Centre and Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
  2. 2Division of Infectious Diseases, Department of Medicine, Harvard Medical School, Harvard School of Public Health, Boston, Massachusetts
  3. 3Tropical and Geographic Medicine Center, Massachusetts General Hospital, Boston, Massachusetts
  4. 4W.C. Gorgas Center for Geographic Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham
  5. 5International Health Program, Yale School of Medicine, New Haven, Connecticut
  6. 6Division of General Pediatric and Adolescent Medicine, Department of Pediatrics, Mayo Clinic College of Medicine and Mayo Eugenio Litta Children's Hospital, Mayo Clinic, Rochester, Minnesota
  7. 7Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
  8. 8Departments of Medicine and Pathology, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville
  9. 9Department of Medicine, University of Toronto and Center for Travel and Tropical Medicine, Toronto General Hospital, Toronto, Ontario, Canada
  1. Reprints or correspondence: Dr. David R. Hill, National Travel Health Network and Centre, London School of Hygiene and Tropical Medicine, Hospital for Tropical Diseases, Mortimer Market Centre, Capper St., London WC1E 6JB, United Kingdom (david.hill{at}uclh.org).

To the Editor—Dr. Connor [1] raises important issues about the use of antibiotics to treat traveler's diarrhea (TD). He highlights the association of fluoroquinolones with the increasing problem of Clostridium difficile–associated diarrhea and its associated morbidity and mortality. He then proposes an alternative approach to the prevention of TD by prescribing prophylactic rifaximin for travelers, with the goal of decreasing the risk of TD and preventing a potential long-term sequela of TD, postinfectious irritable bowel syndrome.

Dr. Connor's letter [1] may be read to imply that the Infectious Diseases Society of America guidelines [2] recommend widespread use of antibiotic prophylaxis with a fluoroquinolone to prevent TD. The guidelines clearly do not endorse this approach. They state that, based on currently available data, antibiotic prophylaxis with any antimicrobial against TD is not recommended for most travelers and should only be prescribed after a careful risk-benefit assessment for an individual traveler [2]. Instead, the guidelines endorse targeted short-course treatment of travelers with TD using antibiotics with demonstrated efficacy for the treatment of a subgroup of individuals.

Dr. Connor [1] also raises the specific concern of whether fluoroquinolones—as opposed to rifaximin—should be used for treatment because of the association of fluoroquinolones in certain contexts with C. difficile–associated diarrhea. The Infectious Diseases Society of America guidelines are in agreement that inappropriate use of all antibiotics should be avoided to reduce the risk of C. difficile–associated diarrhea and other adverse events. The literature regarding the treatment of TD with antibiotics demonstrates that a single dose or 3 days of treatment at most is sufficient for most patients. As to the choice of antibiotic, evidence demonstrates equivalency, if not superiority, of a fluoroquinolone in the treatment of individuals with TD, compared with every other class of antibiotic [3–5]. Data also support the use of azithromycin in individuals for whom fluoroquinolones are contraindicated or who develop TD in areas of the world with a high rate of fluoroquinolone-resistant Campylobacter-associated TD, such as South and Southeast Asia [6]. The use of rifaximin is supported in areas of the world where Escherichia coli–associated diarrhea is common, such as Mexico [3]. Although the introduction of rifaximin provides an alternative antibiotic, there may be potential drawbacks with this agent. It is not recommended for treatment of individuals with diarrhea in whom there is mucosal invasion with a pathogen, such as Shigella species, Campylobacter species, or in some cases, Salmonella species [5, 7]. In addition, although it is felt that the risk of development of resistance to rifaximin may be low, a recent study indicates that resistance can develop during treatment [5]. There is also the theoretical risk that widespread use of rifaximin will further induce resistance.

Finally, Dr. Connor [1] notes that the development of irritable bowel syndrome following TD is a potential reason for considering prophylaxis for most travelers. Although the reported incidence of irritable bowel syndrome at 6 months after TD ranges from 4% to 14% [8–10], the true incidence of this syndrome is not clear, and all contributing factors to the syndrome and its potential prevention have yet to be defined.

The guidelines panel welcomes continued investigation into TD, one of the most common ailments of travelers. Nevertheless, until there is clear supporting evidence to change recommendations, the current Infectious Diseases Society of America guidelines on the management of TD should be followed, including attention to choice of food and beverage and, in the event of diarrhea, prompt self-treatment (hydration, symptom control, and short-course antibiotic treatment in selected patients). At present, chemoprophylaxis should be restricted to well-informed travelers in whom the benefits clearly outweigh the risks.

 
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Acknowledgments

Potential conflicts of interest.F.J.B. has been a paid consultant for Pfizer. P.E.K. has received honoraria for speaking engagements for GlaxoSmithKline and has received honoraria for participation on the advisory board of Sanofi Pasteur. All other authors: no conflicts.

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  1. Clin Infect Dis. (2008) 46 (3): 476-477. doi: 10.1086/526348
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