Realizing that international travel is associated with the acquisition of antibiotic-resistant intestinal flora and wanting to better characterize specific risk factors for that colonization, Finnish investigators evaluated 430 international travelers. Prior to travel, 1% were already colonized with extended-spectrum betalactamase-producing Enterobacteriaceae (ESBL-PE). Following travel, 21% were colonized with ESBL-PE. Of travelers to South Asia, 46% became colonized as compared to 33% of travelers to Southeast Asia, 33% of travelers to North Africa and the Middle East, and 12% of travelers to sub-Saharan Africa. During the study, 67% of travelers had an episode of diarrhea, and 26% of those who developed diarrhea became colonized with ESBL-PE. Of the 18% of travelers with diarrhea who treated the diarrhea with an antibiotic, 46% became ESBL-PE-positive (as opposed to 29% of those who used an antibiotic for something other than diarrhea during the trip). Interestingly, only 6% of pediatric travelers became colonized with ESBL-PE. Based on these results, the authors advise against using antibiotics for mild or moderate travelers’ diarrhea.

COMMENTARY

Multi-drug resistant Gram-negative intestinal organisms are increasingly problematic. Betalactamase-producing organisms have existed for millennia, but extended-spectrum betalactamases were first described in Europe in the 1980s.1 Infections by these organisms are associated with relative increases in both morbidity and mortality in adults.1

A review of pediatric studies during the past decade1 indicates that colonization with ESBL-PE is less common in North America (but increasing form 0.3% in 2000 to 0.9% in 2010) than in Europe (3-7% in France and Sweden, but 24% in Spain). Colonization rates in South America have been around 12%. Among sick patients in Asia and Africa, much higher rates of ESBL-PE are identified.1

Millions of people travel internationally each year, and international travel is a well-recognized risk for acquisition of ESBL-PE. Among travelers returning home to Germany, 30% had acquired ESBL-producing E. coli, and 9% had acquired ESBL-producing Klebsiella pneumoniae.2 In that study, the greatest risk of acquisition of ESBL-PE was with travel to India (73%) and Southeast Asia (48%), and risk was greatest in those who developed diarrhea during their travel.2 In a study from New York, 1.7% of travelers were colonized with ESBL-PE prior to their travel, and 25% acquired ESBL-PE during travel.3

Infections with ESBL-PE are related to increased morbidity and mortality. There is concern that acquisition of ESBL-PE during travel could increase the travelers’ risk of subsequent severe infection and that the resistant organisms could also be spread to post-trip contacts of the travelers. In the New York study, locally acquired ESBL-PE samples from hospitalized patients were not the same organisms as found near the same time in returning travelers.3 However, a Norwegian study reported that recent travel was a risk factor for developing ESBL-PE urinary tract infections.4 Thus, the risk of resistant infection related to travel-associated colonization is real.

How long do travel-acquired ESBL-PE persist? In the German study, only 9% of travelers who acquired ESBL-PE were still positive 6 months later.2 There are real risks of spreading these germs following travel, and travel-related illness has been reported; however, the resistant germs usually do not persist very long after travel.

Certainly, travelers should be advised to apply rigorous food, beverage, and hand hygiene measures. Unfortunately, self-reported compliance with these efforts was not related to any difference in risk of acquiring ESBL-PE in either the Finnish or German2 study.

It is unknown if the choice of antibiotic for treatment of travelers’ diarrhea relates to the risk of colonization with ESBL-PE. However, none of the commonly used presumptive treatments (quinolones, azithromycin) is a beta lactam antibiotic. It is most likely that any antibiotic can alter the underlying intestinal flora so that subsequently ingested ESBL-PE can then colonize the travelers’ intestines. All antibiotic use should be judicious. Previous fluoroquinolone treatment was also a risk factor for ESBL-PE infection in French intensive care unit patients.5

Interestingly, children were less likely to acquire ESBL-PE in the study of Finnish travelers. Of course, this does not mean that children are not at some risk.1 In a study of very low birth weight babies, maternal colonization was a significant risk factor for infant colonization.6

Pending further study, the authors’ caution seems wise as we provide pre-travel consultation. Most bouts of travelers’ diarrhea are self-limited; they are bothersome but not life-threatening. For travelers who develop diarrhea, antibiotics should only be used when truly necessary.

REFERENCES

  1. Lukac PJ, et al. Extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: Old foe, emerging threat. Clin Infect Dis PMID: 2559574, published online 1-16-2015.
  2. Lubbert C, et al. Colonization with extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacteriaceae in international travelers returning to Germany. Int J Medical Microbiology 2015;305:148-156.
  3. Weisenberg SA, et al. Extended spectrum beta-lactamase-producing Enterobacteriaceae in international travelers and non-travelers in New York City. PLoS One 2012;7:e45141.
  4. Soraas A, et al. Risk factors for community-acquired urinary tract infections caused by ESBL-producing enterobacteriaceae - a case-control study in a low prevalence country. PLoS One 2013;8:e69581.
  5. Vodovar D, et al. Predictive factors for extended-spectrum beta-lactamase producing Enterobacteriaceae causing infection among intensive care unit patients with prior colonization. Infection 2014;42:743-748.
  6. Denkel LA, et al. The mother as most important risk factor for colonization of very low birth weight infants with extended-spectrum beta-lactamase-producing Enterobacteriaceae. J Antibicrob Chemother 2014;69:2230-2237.