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Background Extended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies. Methods We used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States. To select candidate features, we used data collected from pre-travel and post-travel questionnaires, alongside destination-specific data from external sources. We utilized LASSO regression for feature selection, followed by random forest or logistic regression modelling, to derive a CPR for ESBL acquisition. Results A CPR using machine learning and logistic regression on 10 features has an internally cross-validated area under the receiver operating characteristic curve (cvAUC) of 0.70 (95% confidence interval 0.69–0.71). We also demonstrate that a four-feature model performs similarly to the 10-feature model, with a cvAUC of 0.68 (95% confidence interval 0.67–0.69). This model uses traveller's diarrhoea, and antibiotics as treatment, destination country waste management rankings and destination regional probabilities as predictors. Conclusions We demonstrate that by integrating traveller characteristics with destination-specific data, we could derive a CPR to identify those at highest risk of acquiring ESBL-PE during international travel. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. Results: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. Conclusion: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. Trial registration: Clinical trial registration number: ClinicalTrials.govNCT01776021. [ABSTRACT FROM AUTHOR]

Escherichia coli is the most common cause of urinary tract infections (UTIs) in children, and yet the underlying mechanisms of virulence and antibiotic resistance and the overall population structure of the species is poorly understood within this age group. To investigate whether uropathogenic E. coli (UPEC) from children who developed pyelonephritis carried specific genetic markers, we generated whole-genome sequence data for 96 isolates from children with UTIs. This included 57 isolates from children with either radiologically confirmed pyelonephritis or cystitis and 27 isolates belonging to the well-known multidrug-resistant sequence type ST131, selected to investigate their population structure and antibiotic resistance characteristics. We observed a UPEC population structure that is similar to those reported in adults. In comparison with prior investigations, we found that the full pap operon was more common among UPEC from pediatric cases of pyelonephritis. Further, in contrast with recent reports that the P-fimbriae adhesin-encoding papGII allele is substantially more prevalent in invasive UPEC from adults, we found papGII was common to both invasive and non-invasive UPEC from children. Among the set of ST131 isolates from children with UTIs, we found antibiotic resistance was correlated with known genetic markers of resistance, as in adults. Unexpectedly, we observed that fimH 30, an allele of the fimbrial gene fimH often used as a proxy to type ST131 isolates into the most drug-resistant subclade C, was carried by some of the subclade A and subclade B isolates, suggesting that the fimH 30 allele could confer a selective advantage for UPEC. IMPORTANCE Urinary tract infections (UTIs), which are most often caused by Escherichia coli , are not well studied in children. Here, we examine genetic characteristics that differentiate UTI-causing bacteria in children that either remain localized to the bladder or are involved in more serious kidney infections. We also examine patterns of antibiotic resistance among strains from children that are part of E. coli sequence type 131, a group of bacteria that commonly cause UTIs and are known to have high levels of drug resistance. This work provides new insight into the virulence and antibiotic resistance characteristics of the bacteria that cause UTIs in children., Competing Interests: The authors declare no conflict of interest.

Background: Culture-based studies have shown that acquisition of extended-spectrum β-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 β-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., Competing Interests: Declaration of interests SET is a Committee Member for the American Society of Transplantation Consensus Conference on Novel Infectious Disease Diagnostics in Solid Organ Transplant, Subgroup Leader on the Rapid Antimicrobial Resistance Detection Methods Subgroup, and received funding within the past 36 months from the Massachusetts General Hospital Vickery-Colvin Grant. DTL is a councillor on Clinical Group, Member of the Scientific Program Committee for American Society of Tropical Medicine and Hygiene, and received authorship royalties from UpToDate. JBH provided editorial services for UpToDate. RCL received payments for editorial services from UpToDate and the US Centers for Disease Control and Prevention Foundation. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes respiratory and invasive infections as well as conjunctivitis. Strains that lack the capsule, a main virulence factor and the target of current vaccines, are often isolated from conjunctivitis cases. Here we perform a comparative genomic analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal codes in the United States. We find that the vast majority of conjunctivitis strains are members of a distinct cluster of closely related unencapsulated strains. These strains possess divergent forms of pneumococcal virulence factors (such as CbpA and neuraminidases) that are not shared with other unencapsulated nasopharyngeal S. pneumoniae. They also possess putative adhesins that have not been described in encapsulated pneumococci. These findings suggest that the unencapsulated strains capable of causing conjunctivitis utilize a pathogenesis strategy substantially different from that described for S. pneumoniae at other infection sites.