The traveller and antimicrobial resistance: what’s new and where are we headed? Free

While global travel patterns during coronavirus disease 2019 (COVID-19) remain on hold and we are all fixated on a virus, vaccination and escape mutants, the existential threat of antimicrobial resistance (AMR) and attributable death and morbidity, which it continues to cause globally looms large.1 In this issue of the Journal, four articles are published that contribute to an updated understanding of the epidemiology of AMR in travellers, the potential role of the microbiome as it relates to risk of colonization with AMR pathobionts, and a relook at practice and behaviour related to stand-by antibiotic (SBA) use.

A number of comprehensive reviews have been published which describe the risk, epidemiology and features of acquisition of extended spectrum beta-lactamase producing Enterobacteriales (ESBL-PE) in travellers.2 Travel to Asia, exposure to medical care while abroad, developing travellers’ diarrhoea (TD) and exposure to antibiotics during travel are all important risk factors.3 Much of these data have been limited to travellers from European regions and a pair of articles in this month’s journal by Buchek et al.4 and Peng et al.5 present additional epidemiological data from unique populations not previously well described. Military service members, often at high risk of environmental exposure, travellers’ diarrhoea, invasive trauma-associated infections, as well as living often in congregate settings are a unique population of travellers for which ESBL-PE colonization during deployment and upon return may represent a challenge. In this issue, a US military research team aimed to understand incidence and risk factors for MDR colonization among personnel travelling internationally for official duty.4 Among a cohort of 64 travellers (accounting for 72 trips) pre- and post-travel rectal swabs were obtained and linked pre- and post-travel survey, incident ESBL-PE colonization occurred in eight (11% of all trips). Travel to South Asia was the only risk factor identified and no risk with TD or use of antimicrobials, including doxycycline for malaria prophylaxis, was observed in this small sample study. However, it would appear that risk of ESBL-PE acquisition may be lower compared to other US and European traveller populations, though future research is needed to understand the impact of colonization to the individual and whether such colonization specifically might impact post-injury infection outcomes in operational settings.

Peng and colleagues5 substantially add to our understanding through a report on a study of a prospective cohort of 90 Hong Kong travellers. Although Hong Kong is a high-income country, 41 (45.6%) travellers who were enrolled pre-travel tested positive for ESBL-PE prior to travel. As travel from low- and middle-income countries (LMIC) to the higher income countries is also on the rise, this is a stark observation which draws attention to the potential of travellers from endemic countries to carry and introduce MDR infections into the communities where they travel. Among the remaining 49 travellers who returned from trips predominantly to LMICs, 20 (40.8%) acquired an incident ESBL-PE colonization. Neither TD nor antibiotic use were associated with increased risk of ESBL-PE acquisition, however eating raw seafood increased risk (odds ratio 3.61, P = 0.039) and interestingly a diarrheal illness in the 3 months prior to travel decreased subsequent risk of ESBL-PE acquisition (10% ESBL-PE incidence in those with diarrhoea 3 months prior to travel vs 51.7% ESBL-PE incidence who did not report diarrhoea in the 3 months prior to travel, P = 0.003). The research team further explored how the host microbiome pre-travel might contribute to risk of ESBL-PE acquisition during travel and noted richness in Actinobacteria and 12 other genera predicted ESBL-PE acquisition with fair accuracy. Many of these genera fell into the category of Bifidobacteria, which are known to be producers of short chain fatty acids and contribute to maintaining gut homeostasis. This may represent a useful strategy for further investigation in prevention of ESBL-PE acquisition, and would appear encouraging given a recent randomized control trial, which demonstrated a reduction of a Bifidobacteria containing formula of eight different living bacterial strains in the reduction of chronic ESBL-PE carriage.6

There are few reported instances recorded where travellers, specifically, have introduced MDR bacteria into a community, which has become sustained. This may not be surprising given the high sanitary conditions of the higher income countries where travellers return. However, one well documented and alarming example is with methicillin resistant Staphylococcus aureus (MRSA) where a strain USA300 was introduced and became endemic in Canada, Venezuela, Colombia and Ecuador.7 Another example being travel associated introduction of drug resistant shigellosis in the UK and US.8,9 Given this issue and noted concern, a research letter by Tran et al.10 describes a prospective cohort study of healthy German travellers that was designed to measure the rates of incident MRSA colonization associated with travel. Of 311 travellers who screened negative for MRSA colonization prior to travel, 196 (63%) travellers who returned a self-collected nasal swab and travel questionnaire were included for assessment of incident MRSA colonization. The population was predominantly pleasure travel, and to LMICs in Africa, the Western Pacific, Central and South America and Southeast Asia for an average of 23 days. Of the 196 travellers, one was identified to have an incident MRSA colonization. While antibiotic use (5%) and care at local health systems (8%) are known risk factors and were relatively rare, the authors conclude that the risk for MRSA colonization is low in healthy travellers. While MRSA incident colonization may be low, it is certain that ESBL-PE colonization is not. Returning to the topic of travellers as potential vehicles to spreading disease and the primary concern of ESBL-PE, such direct evidence has not been described. Given the multi-source modes of introduction and unique settings of expansion and sustainment, efforts to understand and control these infections with and between populations on different continents pose a major challenge and is in need of additional study.11

Finally, Turunen and Kantele12 report a re-analysis of data from a 2008–2010 Finnish cohort of travellers, which aims at describing the rates of justified and unjustified antibiotic use in the framework of various contemporary and historical treatment guidelines. The authors used a strict definition of justified antibiotic use in cases of TD where there was fever and/or disruption or prevention of daily activities. In this re-analysis of data collected over a decade ago, since which recommendations on pre-travel counselling and treatment have changed, 37% of TD treatment were considered justified. A number of important limitations have been previously observed with the study design utilized,13 but it is interesting to note that among those in whom the use of antibiotics would have been justified, only 41% elected to do so. Although there are no data on the outcome, e.g. duration of illness in the remaining 59% the authors concluded that ‘antibiotics are not necessary in all cases of disabling diarrhoea’.

Regardless, these data are an important reminder that more research is needed to fully inform providers on optimized counselling and empowerment of travellers to adhere to evidence-based recommendations and reduce the burdens associated with illness. Careful assessment of the impacts of ESBL-PE on the individual traveller, the communities to which they return and interventions to reduce acquisition or decolonization are urgently needed.

Authors’ contributions

MR drafted initial manuscript. CE and RS provided critical review and editing.

Conflict of interest: None declared.

References