Wey, E. Q. | Search bioRxiv

bioRxiv2025

A metagenomic approach to One Health surveillance of antimicrobial resistance in a UK veterinary centre

IntroductionThere are currently no standardised guidelines for genomic surveillance of One Health (OH) antimicrobial resistance (AMR). This project aimed to utilise metagenomics to identify AMR genes present in a companion animal hospital and compare these with phenotypic results from bacterial isolates from clinical specimens from the same veterinary hospital. MethodsSamples were collected from sites around a primary companion animal veterinary hospital in North London. Metagenomic DNA was sequenced using Oxford Nanopore Technologies (ONT) MinION. The sequencing data were analysed for AMR genes, plasmids and clinically relevant pathogen species. These data were compared to phenotypic speciation and antibiotic susceptibility tests (ASTs) of bacteria isolates from patients. ResultsThe most common resistance genes identified were aph (n=101 times genes were isolated across 48 metagenomic samples), sul (84), blaCARB (63), tet (58) and blaTEM (46). In clinical isolates, a high proportion of phenotypic resistance to the {beta}-lactams was identified. Rooms with the greatest mean number of resistance genes identified per swab site were the medical preparation room, dog ward and surgical preparation room. Twenty-four Gram-positive and four enterobacterial plasmids were identified. Sequencing reads matched with 14/22 (64%) of the phenotypically isolated bacterial species. DiscussionMetagenomics identified AMR genes, plasmids and species of relevance to human and animal medicine. Communal animal-handling areas harboured more AMR genes than areas animals did not frequent. When considering infection prevention and control (IPC) measures, adherence to, and frequency of, cleaning schedules, alongside potentially more comprehensive disinfection of animal-handling areas may reduce the number of potentially harmful bacteria present. PubMed "veterinary" or "companion" AND "AMR" or "resistan*" NOT (Review[Publication Type]) (2018-2023) "veterinary" or "companion" AND "AMR" or "resist*" AND "sequencing" or "metagenomic*" "veterinary" or "companion" AND "AMR" or "resistan*" NOT (Review[Publication Type]) (2018-2023) https://www.iscaid.org/clinical-practice

genomics↗

bioRxiv2024

Quinoline synergy and reduced use: a study of pharmacodynamic interactions

SynopsisO_ST_ABSBackgroundC_ST_ABSMeropenem, gentamicin and ciprofloxacin have been used as empiric broad-spectrum combination therapy in different combinations. Recent restrictions on the use of quinolones jeopardises the rational of administering this combination to increase the spectrum of coverage for this particular case. A mechanistic understanding of pharmacodynamic interaction for these combinations is lacking but can provide insight in the necessity of using the different moieties. ObjectivesTo study pharmacodynamic drug-drug interaction between meropenem, gentamicin and ciprofloxacin against Escherichia coli. MethodsStatic time kill curve experiments were conducted with Escherichia coli (NCTC(R) 12241) at 0.25 - 16 x MIC for a duration of 24 hours with samples being collected at 0, 2, 4, 6, 8, and 24 hour. Meropenem, gentamicin and ciprofloxacin were tested alone, in two- and three-way combinations. Bacterial load time series data were enumerated on Meuller Hinton plates and Colony Forming Unit data was modelled using nonlinear mixed-effects models in nlmixr. ResultsMeropenem, gentamicin and ciprofloxacin two- and three-way combinations prevented regrowth, but did not when these moieties were studied alone. Gentamicin and meropenem were synergistic by decreasing ciprofloxacin IC50 and the combination effects of meropenem and gentamicin and the addition of meropenem on top of a gentamicin and ciprofloxacin combination were indifferent. ConclusionsOur findings emphasize the added value of a quinolone in the drug combination. In light of the recent move towards reduced use of quinolones, a quinolone free combination still prevented regrowth, it just did not display further synergy on IC50 and was indifferent in initial killing.

pharmacology and toxicology↗