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Antibiotics for travelers' diarrhea may lead to spread of superbugs
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The use of antibiotics for diarrhea placed travelers at greater risk for becoming colonized by resistant intestinal bacteria and then transmitting those strains when they return home, according to recent study data published in Clinical Infectious Diseases.
“The great majority of all cases of travelers’ diarrhea are mild and resolve on their own,” study researcher Anu Kantele, MD, PhD, associate professor in infectious diseases at Helsinki University Hospital, Finland, said in a press release.
Kantele and colleagues collected stool samples from 430 Finns before and after traveling outside Scandinavia to determine if they had become colonized by extended-spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae and carbapenemase-producing Enterobacteriaceae. The travelers also completed questionnaires about the use of antimicrobials and other potential risk factors for developing infection.
Results indicated 21% of the travelers had become colonized by ESBL-producing Enterobacteriaceae while abroad, but none had carried carbapenemase-producing Enterobacteriaceae. Significant risk factors for acquiring the drug-resistant bacteria included geographic region, diarrhea, increasing age and antibiotic treatment of diarrhea while abroad.
Among travelers who used antibiotics for diarrhea, 37% were colonized by ESBL-producing Enterobacteriaceae (adjusted OR=3; 95% CI, 1.4-6.7). The risk for colonization was highest among travelers to South Asia, where 80% of those who took antibiotics for diarrhea became colonized. Regions with the next highest risk for travelers included Southeast Asia, East Asia and North Africa/Middle East.
Although none of the 90 study participants who were colonized by ESBL-producing Enterobacteriaceae became infected, the strains of resistant bacteria carried home by international travelers still pose serious risks to the population at-large in developed countries.
“More than 300 million people visit these high-risk regions every year,” Kantele said. “If approximately 20% of them are colonized with the bugs, these are really huge numbers. This is a serious thing. The only positive thing is that the colonization is usually transient, lasting for around half a year.”
Based on these findings, the researchers concluded that valid strategies for the prevention of travelers’ diarrhea and restricted antimicrobial use while traveling abroad are needed to avoid colonization by resistant intestinal bacteria.
In a related editorial, Bradley A. Connor, MD, of Weill Cornell Medical College, and Jay S. Keystone, MD, of Toronto General Hospital, called for updated guidance on what criteria should be used to recommend antibiotics for severe diarrhea while traveling abroad (ie, the presence of fever or other symptoms). They also suggested more study is needed on the effect of travel on gut microflora — including an increased susceptibility to postinfectious irritable bowel syndrome (PI-IBS) — and new approaches to the prevention of travelers’ diarrhea outside of prescribing antibiotics.
“It is clear that antibiotic self-treatment of [travelers’ diarrhea] may contribute to the global spread of [ESBL-producing Enterobacteriaceae] and may be a factor in the etiology of PI-IBS,” they wrote. “Are travel medicine advisors and travelers prepared to change their approach to the management of the single most frequent cause of illness during international travel? Stay tuned!”
For more information:
Connor BA. Clin Infect Dis. 2015;doi:10.1093/cid/ciu961.
Kantele A. Clin Infect Dis. 2015;doi:10.1093/cid/ciu957.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Herbert L. DuPont, MD
In the paper recently published by Kantele et al, the authors showed an association between the use of antibiotics for travelers’ diarrhea while people were in high-risk regions and acquisition of extended-spectrum beta-lactamase–producing Enterobacteriaceae. The study importantly focuses on antibiotic use in travelers as an explanation for the acquisition of resistance.
There are two issues that need to be resolved before understanding the significance of the potentially important findings. They relate to the relationship between the diarrhea episode and acquisition of ESBL resistance, and the specific antibacterial drugs being used in therapy that could contribute to acquisition of resistance. On the first issue it is not clear to this reviewer if the resistance occurred because of antibiotics taken for diarrhea, or if the organisms causing diarrhea along with ingested local flora from contaminated food in the unhygienic environment during bouts of diarrhea were responsible for acquisition of resistance. While the numbers were not large, use of antibiotics in the study for conditions other than travelers’ diarrhea was not associated with acquisition of this resistance, and travelers’ diarrhea in general, without receiving antibiotics, appeared to be associated with acquisition of resistance. From this study, the country where travelers’ diarrhea occurred was an important variable in the acquisition of resistant strains, again suggesting environmental factors were key in the acquisition of resistance.
On the second issue, the specific antimicrobial used for therapy was not studied by the authors. It may be that anti-travelers’ diarrhea drugs differ in terms of risk of developing resistance. It is conceivable that with more study a certain molecule should not be used in therapy while others are acceptable. More study is needed on this very important topic.
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