The Entomopathogenic Bacterial Endosymbionts Xenorhabdus and Photorhabdus: Convergent Lifestyles from Divergent Genomes

Members of the genus Xenorhabdus are entomopathogenic bacteria that associate with nematodes. The nematode-bacteria pair infects and kills insects, with both partners contributing to insect pathogenesis and the bacteria providing nutrition to the nematode from available insect-derived nutrients. The nematode provides the bacteria with protection from predators, access to nutrients, and a mechanism of dispersal. Members of the bacterial genus Photorhabdus also associate with nematodes to kill insects, and both genera of bacteria provide similar services to their different nematode hosts through unique physiological and metabolic mechanisms. We posited that these differences would be reflected in their respective genomes. To test this, we sequenced to completion the genomes of Xenorhabdus nematophila ATCC 19061 and Xenorhabdus bovienii SS-2004. As expected, both Xenorhabdus genomes encode many anti-insecticidal compounds, commensurate with their entomopathogenic lifestyle. Despite the similarities in lifestyle between Xenorhabdus and Photorhabdus bacteria, a comparative analysis of the Xenorhabdus, Photorhabdus luminescens, and P. asymbiotica genomes suggests genomic divergence. These findings indicate that evolutionary changes shaped by symbiotic interactions can follow different routes to achieve similar end points

Global Distribution and Epidemiologic Associations of Escherichia coli Clonal Group A, 1998-2007

Escherichia coli clonal group A (CGA) was first reported in 2001 as an emerging multidrug-resistant extraintestinal pathogen. Because CGA has considerable implications for public health, we examined the trends of its global distribution, clinical associations, and temporal prevalence for the years 1998-2007. We characterized 2,210 E. coli extraintestinal clinical isolates from 32 centers on 6 continents by CGA status for comparison with trimethoprim/sulfamethoxazole (TMP/SMZ) phenotype, specimen type, inpatient/outpatient source, and adult/child host; we adjusted for clustering by center. CGA prevalence varied greatly by center and continent, was strongly associated with TMP/SMZ resistance but not with other epidemiologic variables, and exhibited no temporal prevalence trend. Our findings indicate that CGA is a prominent, primarily TMP/ SMZ-resistant extraintestinal pathogen concentrated within the Western world, with considerable pathogenic versatility. The stable prevalence of CGA over time suggests full emergence by the late 1990s, followed by variable endemicity worldwide as an antimicrobial drug-resistant public health threat

Global Distribution and Epidemiologic Associations of Escherichia coli Clonal Group A,

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Global Distribution and Epidemiologic Associations of Escherichia coli Clonal Group A, 1998-2007

Escherichia coli clonal group A (CGA) was first reported in 2001 as an emerging multidrug-resistant extraintestinal pathogen. Because CGA has considerable implications for public health, we examined the trends of its global distribution, clinical associations, and temporal prevalence for the years 1998-2007. We characterized 2,210 E. coli extraintestinal clinical isolates from 32 centers on 6 continents by CGA status for comparison with trimethoprim/sulfamethoxazole (TMP/SMZ) phenotype, specimen type, inpatient/outpatient source, and adult/child host; we adjusted for clustering by center. CGA prevalence varied greatly by center and continent, was strongly associated with TMP/SMZ resistance but not with other epidemiologic variables, and exhibited no temporal prevalence trend. Our findings indicate that CGA is a prominent, primarily TMP/SMZ-resistant extraintestinal pathogen concentrated within the Western world, with considerable pathogenic versatility. The stable prevalence of CGA over time suggests full emergence by the late 1990s, followed by variable endemicity worldwide as an antimicrobial drug resistant public health threat

Patterns of antimicrobial drug use in veterinary primary care and specialty practice: A 6‐year multi‐institution study

Abstract Background Combatting antimicrobial resistance requires a One Health approach to antimicrobial stewardship including antimicrobial drug (AMD) use evaluation. Current veterinary AMD prescribing data are limited. Objectives To quantify companion animal AMD prescribing in primary care and specialty practice across 3 academic veterinary hospitals with particular focus on third‐generation cephalosporins, fluoroquinolones, and carbapenems. Animals Dogs and cats presented to 3 academic veterinary hospitals from 2012 to 2017. Methods In this retrospective study, AMD prescribing data from 2012 to 2017 were extracted from electronic medical records at each hospital and prescriptions classified by service type: primary care, specialty practice or Emergency/Critical Care (ECC). Hospital‐level AMD prescribing data were summarized by species, service type, AMD class, and drug. Multivariable logistic full‐factorial regression models were used to estimate hospital, year, species, and service‐type effects on AMD prescribing. Estimated marginal means and confidence intervals were plotted over time. Results The probability of systemic AMD prescribing for any indication ranged between 0.15 and 0.28 and was higher for dogs than cats (P < .05) apart from 2017 at hospital 1. Animals presented to primary care were least likely to receive AMDs (dogs 0.03‐0.15, cats 0.03‐0.18). The most commonly prescribed AMD classes were aminopenicillins/β‐lactamase inhibitors (0.02‐0.15), first‐generation cephalosporins (0.00‐0.09), fluoroquinolones (0.00‐0.04), nitroimidazoles (0.01‐0.06), and tetracyclines (0.00‐0.03). Among the highest priority classes, fluoroquinolones (dogs 0.00‐0.09, cats 0.00‐0.08) and third‐generation cephalosporins (dogs 0.00‐0.04, cats 0.00‐0.05) were most frequently prescribed. Conclusions and Clinical Importance Antimicrobial drug prescribing frequencies were comparable to previous studies. Additional stewardship efforts might focus on fluoroquinolones and third‐generation cephalosporins

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites.

BACKGROUND:Patient-reported outcome metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology. OBJECTIVE:We sought to understand (1) the potential of caregiver report to predict patient self-reported symptoms and (2) the correlation of patient-reported outcome domains with histology. METHODS:Patients with EoE (n = 310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) by using the Pediatric Eosinophilic Esophagitis Symptom Score, version 2 (PEESSv2.0), and the Pediatric QOL EoE module (PedsQL-EoE), and biopsy specimens were analyzed by using the EoE Histology Scoring System. RESULTS:PEESSv2.0 parental and child reports aligned across all domains (r = 0.68-0.73, P &lt; .001). PedsQL-EoE reports correlated between parents and children across ages and multiple domains (r = 0.48-0.79, P &lt; .001). There was a tight correlation between symptoms on PEESSv2.0 and their effects on QOL both on self-report and parental report (P &lt; .001). Self-reported symptoms on PEESSv2.0 (positively) and PedsQL-EoE (inversely) showed a weak correlation with proximal, but not distal, peak eosinophil counts and features and architectural tissue changes on the EoE Histology Scoring System (P &lt; .05). CONCLUSIONS:Parents of children with EoE aged 3 to 18 years accurately reflected their children's disease symptoms and QOL. Self- and parent-reported symptoms correlate with proximal esophageal histology. Our data suggest that parental report in young children can function as an adequate marker for self-reported symptoms and that self-reported symptoms can reflect changes in tissue histology in the proximal esophagus. These findings should be considered during clinical trials for drug development