Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis.

BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum ß-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum ß-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10-10) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10-11) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases.

Global TravEpiNet: a national consortium of clinics providing care to international travelers--analysis of demographic characteristics, travel destinations, and pretravel healthcare of high-risk US international travelers, 2009-2011.

BACKGROUND: International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness. METHODS: We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011. RESULTS: The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low- or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelers were visiting malaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported ≥1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers' diarrhea. Hepatitis A and typhoid were the most frequently administered vaccines. CONCLUSIONS: Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel.

Acquisition and Long-term Carriage of Multidrug-Resistant Organisms in US International Travelers.

We performed prospective screening of stool for multidrug-resistant organisms from 608 US international travelers and identified an acquisition rate of 38% following travel. Carriage rates remained significantly elevated for at least 6 months post-travel. Travel-related diarrhea was a risk factor for acquisition, as well as for long-term carriage upon return.

Impact of Race Versus Education and Race Versus Income on Patients' Motivation to Participate in Clinical Trials.

Our study investigates whether levels of motivation and barriers to participation in clinical trials vary with patients' education and income. A self-administered survey asked outpatients to rank potential influential factors on a "0" to "4" significance scale for their motivation to participate in clinical trials. Principal component analysis (PCA), analysis of variance (ANOVA), Kruskal-Wallis, and Mann-Whitney U tests analyzed the impact of race, education, and income on their motivation to participate. Analysis included 1841 surveys; most respondents had a high school education or some college, and listed annual income < $30,000. There was a significant interaction between race and income on our motivation scale 1 scores (p = .0261). Compared with their counterparts, subjects with less education/lower income ranked monetary compensation (p = .0420 and p < .0001, respectively) as a higher motivator. Minorities and patients with less education and lower income appear to be more influenced by their desire to please the doctor, the race and sex of the doctor, and the language spoken by the doctor being the same as theirs. For all races, education appeared to have a direct relationship with motivation to participate, except for African-Americans, whose motivation appeared to decline with more education. Income appeared to have an inverse relationship with motivation to participate for all races.

Factors Influencing Participation in Clinical Trials: Emergency Medicine vs. Other Specialties.

INTRODUCTION: This study investigated factors that influence emergency medicine (EM) patients' decisions to participate in clinical trials and whether the impact of these factors differs from those of other medical specialties. METHODS: A survey was distributed in EM, family medicine (FM), infectious disease (ID), and obstetrics/gynecology (OB/GYN) outpatient waiting areas. Eligibility criteria included those who were 18 years of age or older, active patients on the day of the survey, and able to complete the survey without assistance. We used the Kruskal-Wallis test and ordinal logistic regression analyses to identify differences in participants' responses. RESULTS: A total of 2,893 eligible subjects were approached, and we included 1,841 surveys in the final analysis. Statistically significant differences (p≤0.009) were found for eight of the ten motivating factors between EM and one or more of the other specialties. Regardless of a patient's gender, race, and education, the relationship with their doctor was more motivating to patients seen in other specialties than to EM patients (FM [odds ratio {OR}:1.752, 95% confidence interval {CI}{1.285-2.389}], ID [OR:3.281, 95% CI{2.293-4.695}], and OB/GYN [OR:2.408, 95% CI{1.741-3.330}]). EM's rankings of "how well the research was explained" and whether "the knowledge learned would benefit others" as their top two motivating factors were similar across other specialties. All nine barriers showed statistically significant differences (p≤0.008) between EM and one or more other specialties. Participants from all specialties indicated "risk of unknown side effects" as their strongest barrier. Regardless of the patients' race, "time commitment" was considered to be more of a barrier to other specialties when compared to EM (FM [OR:1.613, 95% CI{1.218-2.136}], ID [OR:1.340, 95% CI{1.006-1.784}], or OB/GYN [OR:1.901, 95% CI{1.431-2.526}]). Among the six resources assessed that help patients decide whether to participate in a clinical trial, only one scored statistically significantly different for EM (p<0.001). EM patients ranked "having all material provided in my own language" as the most helpful resource. CONCLUSION: There are significant differences between EM patients and those of other specialties in the factors that influence their participation in clinical trials. Providing material in the patient's own language, explaining the study well, and elucidating how their participation might benefit others in the future may help to improve enrollment in EM-based clinical trials.

Nosocomially acquired Pseudomonas stutzeri brain abscess in a child: case report and review.

Pseudomonas stutzeri is a rare cause of nosocomial infection. We report a pediatric case of nosocomially acquired P. stutzeri brain abscess after subdural grid implantation before surgery for refractory epilepsy and review the literature.

Racial Differences Among Factors Associated with Participation in Clinical Research Trials.

OBJECTIVE: To identify whether racial differences exist among various factors associated with patients' decision to participate in clinical research trials. METHODS: A self-administered, IRB-approved survey was utilized with inclusion criteria requiring subjects to be 18 years of age or older, having active patient status and ability to complete the survey without assistance. Subjects were asked to rate potential influential motivators, barriers, and facilitators on a "no influence" (0) to "most influence" (4) scale for participation in research that tests a new drug or device. Kruskal-Wallis testing was used to identify factors significantly associated with race. RESULTS: Analysis included 1643 surveys: 949 (57.8 %) Caucasian; 217 (13.2 %) African-American; 317 (19.3 %) Hispanic; 62 (3.8 %) Multiracial; and 98 (6.0 %) "Other" minorities. Statistically significant differences (p ≤ .02) by race were found for five out of ten motivating factors. "How well the research study is explained to me" had the highest mean value for all races except other minorities, for whom "Knowledge learned from my participation will benefit someone in the future" scored highest. "Risk of unknown side-effects" was the greatest barrier for all races. CONCLUSION: Racial differences exist not only between Caucasians and Minorities for the factors associated with their clinical trial participation, but also among different minority races themselves. To promote diversity in research, recruitment strategies for each individual race should be customized based on what matters to the target population.

Using Locally Derived Seroprevalence Data on Measles, Mumps, Rubella, and Varicella by Birth Cohort to Determine Risks for Vaccine-Preventable Diseases During International Travel.

BACKGROUND: Measles, mumps, rubella, and varicella (MMRV) were common childhood diseases in the United States prior to the introduction of their respective vaccines. Measles was declared eliminated in the United States in 2000. However, 628 cases were reported in 2014, the majority of which have been linked to international travel. The study team set out to investigate the seroprevalence of MMRV in our local population to determine whether such a process can lead to meaningful recommendations for assessing travelers at risk. METHODS: We conducted a cross-sectional seroprevalence study using a quota sampling method. A total of 460 leftover serum samples were collected from individuals born prior to 1996, who live in the Lehigh Valley region of southeast Pennsylvania. The samples were allocated to five birth-year cohorts, and the seroprevalence of each cohort to MMRV was compared. Additionally, overall seroprevalence of each disease was compared with data from prior national studies. Gender differences within each birth cohort were also assessed. RESULTS: The overall seroprevalence values of measles, mumps, rubella, and varicella were 85.8, 82.8, 96.6, and 97.4%, respectively. There were significant associations between seroprevalence and birth cohort for measles (p = 0.01) as well as mumps (p = 0.037). The overall seroprevalence for our study sample was significantly different from the national seroprevalence results of measles, mumps, and rubella. CONCLUSIONS: Our study showed dramatically lower immunity rates for measles and mumps than those shown by prior national seroprevalence studies. The rates in many of the later birth cohorts born after 1966 were significantly lower than the rates reported as necessary to sustain herd immunity. Given that patients' immunization records are not always available or complete, collecting local seroprevalence data may be necessary to more accurately recommend antibody testing and vaccination during pre-travel assessments.

Pseudomonas aeruginosa causing a right carotid artery mycotic aneurysm after a dental extraction procedure.

Mycotic aneurysms of the carotid arteries are rare. We describe a right carotid artery mycotic aneurysm in a 70-year-old man. His symptoms began immediately after a complicated molar extraction and persisted until the diagnosis was made and surgical resection and repair were undertaken. Pseudomonas aeruginosa was isolated from multiple blood cultures and excised tissues. We review another 73 cases uncovered by an extensive literature search. Bacteremia, recent surgery, head and neck infections, dental infections, and endocarditis are the most common predisposing conditions. Computed tomography and magnetic resonance imaging are techniques for accurately confirming the suspicion of any aneurysm, but angiography is the gold standard. Primary resection of the aneurysm with native vein interposition, in conjunction with prolonged antibiotic therapy, is the preferred strategy. A total of 6 cases thus far, including ours, have been clearly associated with dental surgical procedures. These cases are characterized by rapidly enlarging neck masses in the presence of fever. Microorganisms, particularly gram-negative rods, in contrast to normal oral flora, eg, streptococci and anaerobes, are often isolated. With prompt diagnosis and treatment, outcome is often satisfactory.

Pre-exposure rabies vaccination among US international travelers: findings from the global TravEpiNet consortium.

BACKGROUND: People who travel to areas with high rabies endemicity and have animal contact are at increased risk for rabies exposure. We examined characteristics of international travelers queried regarding rabies vaccination during pretravel consultations at Global TravEpiNet (GTEN) practices during 2009-2010. MATERIAL AND METHODS: We performed bivariate and multivariable analyses of data collected from 18 GTEN clinics. Travel destinations were classified by strength level of rabies vaccination recommendation. RESULTS: Of 13,235 travelers, 226 (2%) reported previous rabies vaccination, and 406 (3%) received rabies vaccine at the consultation. Common travel purposes for these 406 travelers were leisure (26%), research/education (17%), and nonmedical service work (14%). Excluding the 226 who were previously vaccinated, 8070 (62%) of 13,009 travelers intended to visit one or more countries with a strong recommendation for rabies vaccination; 1675 (21%) of these 8070 intended to travel for 1 month or more. Among these 1675 travelers, 145 (9%) were vaccinated, 498 (30%) declined vaccination, 832 (50%) had itineraries that clinicians determined did not indicate vaccination, and 200 (12%) remained unvaccinated for other reasons. In both bivariate and multivariate analyses, travelers with trip durations >6 months versus 1-3 months (adjusted odds ratio [OR]=4.9 [95% confidence interval [CI] 2.1, 11.4]) and those traveling for "research/education" or to "provide medical care" (adjusted OR=5.1 [95% CI 1.9, 13.7] and 9.5 [95% CI 2.2, 40.8], respectively), compared with leisure travelers, were more likely to receive rabies vaccination. CONCLUSIONS: Few travelers at GTEN clinics received rabies vaccine, although many planned trips 1 month long or more to a strong-recommendation country. Clinicians often determined that vaccine was not indicated, and travelers often declined vaccine when it was offered. The decision to vaccinate should take into account the strength of the vaccine recommendation at the destination country, duration of stay, availability of postexposure prophylaxis, potential for exposure to animals, and likelihood of recurrent travel to high-risk destinations.

A quality improvement initiative using a novel travel survey to promote patient-centered counseling.

BACKGROUND: We sought to evaluate and provide better itinerary-specific care to precounseled travelers and to assess diseases occurring while traveling abroad by surveying a community population. An additional quality improvement initiative was to expand our post-travel survey to be a more valuable tool in gathering high-quality quantitative data. METHODS: From de-identified data collected via post-travel surveys, we identified a cohort of 525 patients for a retrospective observational analysis. We analyzed illness encountered while abroad, medication use, and whether a physician was consulted. We also examined itinerary variables, including continents and countries visited. RESULTS: The 525 post-travel surveys collected showed that the majority of respondents traveled to Asia (31%) or Africa (30%). The mean number of travel days was 21.3 (median, 14). Univariate analysis demonstrated a statistically significant increase of risk for general illness when comparing travel duration of less than 14 days to greater than 14 days (11.3% vs 27.7%, p < 0.001). Duration of travel was also significant with regard to development of traveler's diarrhea (TD) (p = 0.0015). Destination of travel and development of traveler's diarrhea trended toward significance. Serious illness requiring a physician visit was infrequent, as were vaccine-related complications. CONCLUSIONS: Despite pre-travel counseling, traveler's diarrhea was the most common illness in our cohort; expanded prevention strategies will be necessary to lower the impact that diarrheal illness has on generally healthy travelers. Overall rates of illness did not vary by destination; however, there was a strong association between duration of travel and likelihood of illness. To further identify specific variables contributing to travel-related disease, including patient co-morbidities, reason for travel, and accommodations, the post-travel survey has been modified and expanded. A limitation of this study was the low survey response rate (18%); to improve the return rate, we plan to implement supplemental modalities including email and a web-based database.