Abstract
Infections caused by multidrug-resistant organisms (MDRO) lead to considerable morbidity and mortality. The elderly population residing in nursing homes are a major reservoir of MDRO. Our objective was to characterize the fecal microbiome of 82 elderly subjects from 23 nursing homes and compare their resistome to that of healthy young persons. Comparisons of microbiome composition and the resistome between subjects who acquired MDRO or not were analyzed to characterize specific microbiome disruption indices (MDI) associated with MDRO acquisition. An approach based on both 16S rRNA amplicon and whole metagenome shotgun (WMS) sequencing data was used. The microbiome of the study cohort was substantially perturbed, with Bacteroides, Firmicutes, and Proteobacteria predominating. Compared to healthy persons, the cohort of elderly persons had an increased number, abundance, and diversity of antimicrobial resistance genes. High proportions of study subjects harbored genes for multidrug-efflux pumps (96%) and linezolid resistance (52%). Among the 302 antimicrobial resistance gene families identified in any subject, 60% were exclusively detected within the study cohort, including Class D beta-lactamase genes. Subjects who acquired MDRO or not had significant differences in bacterial taxa; Odoribacter laneus, and Akkermansia muciniphila were significantly greater among subjects who did not acquire MDRO whereas Blautia hydrogenotrophica predominated among subjects who acquired MDRO. These findings suggest that specific MDI may identify persons at high risk of acquiring MDRO.
Highlights
Rates of infections caused by multidrug-resistant organisms (MDRO), including methicillinresistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and multidrugresistant gram-negative bacteria (MDRGN) continue to increase worldwide (Diekema et al, 2019)
One sample was excluded from downstream analysis as it provided less than 1,500 reads
The fecal microbiome of our study cohort was characterized by reduced microbial diversity and enrichment with pathogenic bacteria, suggesting that significant imbalances occur in the gut microbiome of elderly subjects exposed to antimicrobials
Summary
Rates of infections caused by multidrug-resistant organisms (MDRO), including methicillinresistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and multidrugresistant gram-negative bacteria (MDRGN) continue to increase worldwide (Diekema et al, 2019). Since exposure to antimicrobials is among the greatest risk factor for the emergence and spread of MDRO (Joint Commission on Hospital Accreditation, 2016), decreasing unnecessary antimicrobial use is a major focus. Despite such interventions, MDRO rates continue to rise, and novel approaches are needed. Intestinal domination by Enterococcus spp. and Proteobacteria, defined as >30% of the microbiome, increased the risk of vancomycin-resistant enterococcal bacteremia by 9-fold and gram-negative rod bacteremia by 5-fold, respectively, (Taur et al, 2012) Particular taxa, such as Lactobacillus spp. have been associated with protective effects against MDRO colonization (Araos et al, 2016). A recent randomized double-blinded, placebo-controlled trial of a microbiota-based drug, RBX2660, was promising in the prevention of recurrent Clostridioides difficile infection (Dubberke et al, 2018)
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