Acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage after exposure to systemic antimicrobials during travel: systematic review and meta-analysis
Authors: Wuerz Terence C. , Kassim Sameer S. , Atkins Katherine E. 
Published: September 2019

ABSTRACTBackgroundInternational travel is an important risk factor for colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Antimicrobial use during travel likely amplifies this risk, yet to what extent, and whether it varies by antimicrobial class, has not been established.MethodsWe conducted a systematic review that included prospective cohorts reporting both receipt of systemic antimicrobials and acquired ESBL-PE isolated from stool or rectum during international travel. We performed a random effects meta-analysis to estimate odds of acquiring ESBL-PE due to antimicrobials during travel, overall and by antimicrobial class.ResultsFifteen studies were included. The study population was mainly female travellers from high income countries recruited primarily from travel clinics. Participants travelled most frequently to Asia and Africa with 10% reporting antimicrobial use during travel. The combined odds ratio (OR) for ESBL-PE acquisition during travel was 2.37 for antimicrobial use overall (95% confidence interval [CI], 1.69 to 3.33), but there was substantial heterogeneity between studies. Fluoroquinolones were the antibiotic class associated with the highest combined OR of ESBL-PE acquisition, compared to no antimicrobial use (OR 4.68, 95% CI, 2.34 to 9.37).ConclusionsThe risk of ESBL-PE colonization during travel is increased substantially with exposure to antimicrobials, especially fluoroquinolones. While a small proportion of colonized individuals will develop a resistant infection, there remains the potential for onward spread among returning travellers. Public health efforts to decrease inappropriate antimicrobial usage during travel are warranted.Research in contextEvidence before this studyAntimicrobial resistance (AMR) among bacteria that commonly cause human infection is of increasing public health concern. International travel has recently been associated with colonization with Extended-Spectrum Beta-Lactamase Producing-Enterobacteriaceae (ESBL-PE), increasing the spread of drug resistance among these important pathogens. We searched Pubmed, Embase, MEDLINE, Web of Science, SCOPUS, and the Cochrane Library for prospective cohort studies published between January 2000 and June 2018, reporting on acquisition of ESBL-PE among travellers, which reported on antimicrobial use during travel. 15 studies were included, which were at moderate risk of bias. The pooled odds ratio for acquisition of ESBL-PE during travel was 2.37 among antimicrobial users, compared to non-users (95% CI, 1.69 to 3.33). The magnitude of this association was stronger among travellers reporting fluoroquinolone use (OR 4.68, 95% CI 2.34 to 9.37).Added value of this studyThis is the first study to quantify the association between antimicrobial use during travel, overall and by specific antimicrobial class, with ESBL-PE acquisition across broad populations of travellers and destination countries.Implications of all the available evidenceFurther study into the mechanisms by which antimicrobials, such as fluoroquinolones, contribute to AMR may identify protective measures. Meanwhile, antimicrobial use during travel for prevention or treatment of mild-to-moderate traveller’s diarrhea should not be recommended routinely. Where indicated, alternatives to fluoroquinolone antimicrobials should be considered.