The Import and Spread of Antibiotic-Resistant Enterobacteriaceae by Healthy Travellers

Background
International travel contributes to the dissemination of antimicrobial resistance. We examined the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) during international travel, with a focus on predictive factors for acquisition, duration of colonisation and probability of onward transmission. The presented data were published before in The Lancet Infectious Diseases.
Methods
Within the prospective multicenter COMBAT study, 2001 Dutch travellers and 215 non-travelling household members were enrolled. Faecal samples and questionnaires on demographics, illnesses, and behavior were collected before and immediately after travel, and at 1, 3, 6 and 12 months after return. Samples were screened for the presence of ESBL-E. In post-travel samples, ESBL genes were sequenced and PCR with specific primers for plasmid-encoded beta-lactamase enzymes TEM, SHV, and CTX-M group 1, 2, 8, 9, and 25 were used to confirm the presence of ESBL genes in follow-up samples. Multivariable regression analyses and mathematical modelling were used to identify predictors for acquisition and sustained carriage, and to determine household transmission rates.
Findings
633 (34.3%) of 1847 travellers who were ESBL negative before travel and had available samples after return had acquired ESBL-E during international travel (95% CI 32.1-36.5%, with the highest number of acquisitions being among those who travelled to southern Asia in 136 of 181 (75.1%, 95% CI 68.4-80.9%). Important predictors for acquisition of ESBL-E were antibiotic use during travel (adjusted odds ratio 2.69, 95% CI 1.79—4.05), traveller’s diarrhoea that persisted upon return (2.31, 95% CI 1.42-3.76), and pre-existing chronic bowel disease (2.10, 1.13-3.90). The median duration of colonisation after travel was 30 days (95% CI 29-33). 65 (11·3%) of 577 remained colonised at 12 months. CTX-M enzyme group 9 ESBLs were associated with a significantly increased risk of sustained carriage (median duration 75 days; 95% CI 48-102, p=0.0001). Onward transmission was found in 13 (7.7%) of 168 household members. The probability of transmitting ESBL-E to another household member was 12% (95% CI 5-18).
Interpretation
Acquisition and spread of ESBL-E during and after intercontinental travel was substantial and worrisome. Travellers to areas with a high risk for ESBL-E acquisition should be considered as potential carriers of ESBL-E for up to 12 months after return.