Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

Abstract

Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.

Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract – a systematic review

“…Only a few studies have addressed this question since 2020. In line with earlier reviews on the same topic [ 16 , 17 , 34 , 35 ], decolonisation rates varied greatly. Although only two studies reported decolonisation rates for CRE and VRE separately and sample sizes were small, decolonisation rates were higher for CRE patients, with a large effect size compared to controls.…”

Microcin MccI47 selectively inhibits enteric bacteria and reduces carbapenem-resistant Klebsiella pneumoniae colonization in vivo when administered via an engineered live biotherapeutic

“…Additionally, these drugs also cause profound gastrointestinal dysbiosis of the protective microbiota, leaving treated individuals with often dangerous secondary outcomes [47]. Selective decolonization of pathogenic bacteria as a way to minimize their translocation and horizontal transmission to other patients is currently being explored in the pharmaceutical industry by assembling consortia of isolated bacteria that display decolonizing properties against certain species, including K. pneumoniae [48]. However, to our knowledge there is no biotherapeutic yet that has reach stage for human trials.…”

Longitudinal effects of antibiotics and fecal transplant on lemur gut microbiota structure, associations, and resistomes

“…The resulting unassembled sequencing reads underwent multi-kingdom microbiome analysis and profiling of antibiotic resistance genes using the CosmosID bioinformatics platform (CosmosID Inc., Rockville, MD), as described elsewhere 107,108 . The antibiotic resistance and virulence genes in the microbiome were identified by querying the unassembled sequence reads against the CosmosID-curated antibiotic resistance and virulence associated gene databases 109,110 .…”