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Intestinal commensal bacteria can inhibit dense colonization of the gut by vancomycin-resistant Enterococcus faecium (VRE), a leading cause of hospital-acquired infections 1 , 2 . A four-strained consortium of commensal bacteria that contains Blautia producta BP SCSK can reverse antibiotic-induced susceptibility to VRE infection 3 . Here we show that BP SCSK reduces growth of VRE by secreting a lantibiotic that is similar to the nisin-A produced by Lactococcus lactis . Although the growth of VRE is inhibited by BP SCSK and L. lactis in vitro, only BP SCSK colonizes the colon and reduces VRE density in vivo. In comparison to nisin-A, the BP SCSK lantibiotic has reduced activity against intestinal commensal bacteria. In patients at high risk of VRE infection, high abundance of the lantibiotic gene is associated with reduced density of E. faecium . In germ-free mice transplanted with patient-derived faeces, resistance to VRE colonization correlates with abundance of the lantibiotic gene. Lantibiotic-producing commensal strains of the gastrointestinal tract reduce colonization by VRE and represent potential probiotic agents to re-establish resistance to VRE. The gut commensal Blautia producta secretes a lantibiotic that reduces colonization of the gut by the major pathogen vancomycin-resistant Enterococcus faecium , and transplantation of microbiota with high abundance of the lantibiotic gene enhances resistance to colonization in mice.

In this prospective study, we monitored 4 epidemiologically important pathogens (EIPs): methicillin-resistane Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Clostridium difficile, and multidrug-resistant (MDR) Acinetobacter to assess the effectiveness of 3 enhanced disinfection strategies for terminal room disinfection against standard practice. Our data demonstrated that a decrease in room contamination with EIPs of 94% was associated with a 35% decrease in subsequent patient colonization and/or infection.

A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Clostridioides difficile infection (CDI) is most commonly diagnosed using nucleic acid amplification tests (NAAT); the low positive predictive value of these assays results in patients colonized with C. difficile unnecessarily receiving CDI treatment antibiotics. The risks and benefits of antibiotic treatment in individuals with such cases are unknown. Fecal samples of NAAT-positive, toxin enzyme immunoassay (EIA)-negative patients were collected before, during, and after randomization to vancomycin ( n  = 8) or placebo ( n  = 7). C. difficile and antibiotic-resistant organisms (AROs) were selectively cultured from fecal and environmental samples. Shotgun metagenomics and comparative isolate genomics were used to understand the impact of oral vancomycin on the microbiome and environmental contamination. Overall, 80% of placebo patients and 71% of vancomycin patients were colonized with C. difficile posttreatment. One person randomized to placebo subsequently received treatment for CDI. In the vancomycin-treated group, beta-diversity ( P =  0.0059) and macrolide-lincosamide-streptogramin (MLS) resistance genes ( P =  0.037) increased after treatment; C. difficile and vancomycin-resistant enterococci (VRE) environmental contamination was found in 53% of patients and 26% of patients, respectively. We found that vancomycin alters the gut microbiota, does not permanently clear C. difficile , and is associated with VRE colonization/environmental contamination. (This study has been registered at ClinicalTrials.gov under registration no. NCT03388268.) IMPORTANCE A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Existing data suggest most of these patients do not have CDI, but most are treated with oral vancomycin. Potential benefits to treatment include a decreased risk for adverse outcomes if the patient does have CDI and the potential to decrease C. difficile shedding/transmission. However, oral vancomycin perturbs the intestinal microbiota and promotes antibiotic-resistant organism colonization/transmission. We conducted a double-blinded randomized controlled trial to assess the risk-benefit of oral vancomycin treatment in this population. Oral vancomycin did not result in long-term clearance of C. difficile , perturbed the microbiota, and was associated with colonization/shedding of vancomycin-resistant enterococci. This work underscores the need to better understand this population of patients in the context of C. difficile /ARO-related outcomes and transmission.

Patients with hematological malignancies or undergoing hematopoietic stem cell transplantation are vulnerable to colonization and infection with multidrug-resistant organisms, including vancomycin-resistant Enterococcus faecium (VREfm). Over a 10-y period, we collected and sequenced the genomes of 110 VREfm isolates from gastrointestinal and blood cultures of 24 pediatric patients undergoing chemotherapy or hematopoietic stem cell transplantation for hematological malignancy at St. Jude Children’s Research Hospital. We used patient-specific reference genomes to identify variants that arose over time in subsequent gastrointestinal and blood isolates from each patient and analyzed these variants for insight into how VREfm adapted during colonization and bloodstream infection within each patient. Variants were enriched in genes involved in carbohydrate metabolism, and phenotypic analysis identified associated differences in carbohydrate utilization among isolates. In particular, a Y585C mutation in the sorbitol operon transcriptional regulator gutR was associated with increased bacterial growth in the presence of sorbitol. We also found differences in biofilm-formation capability between isolates and observed that increased biofilm formation correlated with mutations in the putative E. faecium capsular polysaccharide (cps) biosynthetic locus, with different mutations arising independently in distinct genetic backgrounds. Isolates with cps mutations showed improved survival following exposure to lysozyme, suggesting a possible reason for the selection of capsule-lacking bacteria. Finally, we observed mutations conferring increased tolerance of linezolid and daptomycin in patients who were treated with these antibiotics. Overall, this study documents known and previously undescribed ways that VREfm evolve during intestinal colonization and subsequent bloodstream infection in immunocompromised pediatric patients.

Gastrointestinal colonization by the nosocomial pathogen vancomycin-resistant Enterococcus faecium (VREfm) can lead to bloodstream infections with high mortality rates. Shifts in VREfm lineages found within healthcare settings occur, but reasons underlying these changes are not understood. Here we sequenced 710 VREfm clinical isolates collected between 2017 and 2022 from a large tertiary care centre. Genomic analyses revealed a polyclonal VREfm population, although 46% of isolates formed genetically related clusters, suggesting a high transmission rate. Comparing these data to a global collection of 15,631 publicly available VREfm genomes collected between 2002 and 2022 identified replacement of the sequence type (ST) 17 VREfm lineage by emergent ST80 and ST117 lineages at the local and global level. Comparative genomic and functional analyses revealed that emergent lineages encoded bacteriocin T8, which conferred a competitive advantage over bacteriocin T8-negative strains in vitro and upon colonization of the mouse gut. Bacteriocin T8 carriage was also strongly associated with strain emergence in the global genome collection. These data suggest that bacteriocin T8-mediated competition may have contributed to VREfm lineage replacement. Genomic and functional analyses of healthcare-associated vancomycin-resistant Enterococcus faecium reveal that bacteriocin T8 is enriched in emergent lineages and provides a competitive advantage in vitro and in vivo.

Today, there is a continuous worldwide battle against antimicrobial resistance (AMR) and that includes vancomycin-resistant enterococci (VRE). Methods that can adequately and quickly detect transmission chains in outbreaks are needed to trace and manage this problem fast and cost-effectively. In this study, DNA-microarray-based technology was developed for this purpose. It commenced with the bioinformatic design of specific oligonucleotide sequences to obtain amplification primers and hybridization probes. Microarrays were manufactured using these synthesized oligonucleotides. A highly parallel and stringent labeling and hybridization protocol was developed and employed using isolated genomic DNA from previously sequenced (referenced) clinical VRE strains for optimal sensitivity and specificity. Microarray results showed the detection of virulence, resistance, and species-specific genes in the VRE strains. Theoretical predictions of the microarray results were also derived from the sequences of the same VRE strain and were compared to array results while optimizing protocols until the microarray result and theoretical predictions were a match. The study concludes that DNA microarray technology can be used to quickly, accurately, and economically detect specifically and massively parallel target genes in enterococci.

We investigated genomic evolution of vancomycin-resistant Enterococcus faecium (VREF) during an outbreak in Shenzhen, China. Whole-genome sequencing revealed 2 sequence type 80 VREF subpopulations diverging through insertion sequence-mediated recombination. One subpopulation acquired more antimicrobial resistance and carbohydrate metabolism genes. Persistent VREF transmission underscores the need for genomic surveillance to curb spread.

Vancomycin-resistant Enterococci (VRE) are major pathogens causing nosocomial infections globally. This study investigated the genetic characteristics of vancomycin-resistant Enterococcus faecium (VREfm) in Thailand between June and November 2022. Fifty-two clinical VREfm isolates from Bangkok hospitals were analyzed for antimicrobial susceptibility, resistance genes, virulence factors, and genotypes using multilocus sequence typing (MLST). Phylogenetic analysis and goeBURST assessed genetic relationships and population structure. The VRE detection rate was 14.5%, with 97.1% E. faecium and 2.9% E. faecalis , likely reflecting the impact of an active case-finding program. All isolates exhibited resistance to penicillin, ampicillin, vancomycin, levofloxacin, ciprofloxacin, and rifampin. Resistance to erythromycin, high-level streptomycin, teicoplanin, and tetracycline occurred in 98.1%, 53.8%, 51.9%, and 17.3% of isolates, respectively. Chloramphenicol, linezolid, and high-level gentamicin remained effective against all isolates. The van A gene was the sole resistance determinant detected. Virulence genes esp and hyl were present in 100% and 88.5% of isolates, respectively. MLST identified five sequence types (STs), with ST17 (86.5%) as the dominant lineage, followed by ST262 (7.7%), ST202, ST787, and ST80 (1.9% each). All isolates belonged to Clonal Complex 17. Genome analysis revealed various resistance genes (VanHAX, aac (6')-Ii, aad (6), ant(6)-Ia , msr C, and tet M) and virulence factors ( acm , bop D, cps A/ upp S, cps B/ cds A, ebp A, ebp B, ebp C, efa A, esp , sgr A, and srt C). The van A gene primarily drives vancomycin resistance in Thailand’s VREfm. Genome analysis reveals antibiotic resistance genes, virulence factors, and mobile genetic elements that may drive antimicrobial resistance, increase diversity, and support adaptation in hospital settings. Ongoing infection control and active surveillance are essential.

Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.

The spread of vancomycin-resistant enterococci (VRE) is a major threat in nosocomial settings. A large-scale multiclonal VRE outbreak has rarely been reported in Japan due to low VRE prevalence. We evaluated the transmission of vancomycin resistance in a multiclonal VRE outbreak, conducted biological and genomic analyses of VRE isolates, and assessed the implemented infection control measures. In total, 149 patients harboring VanA-type VRE were identified from April 2017 to October 2019, with 153 vancomycin-resistant Enterococcus faecium isolated being grouped into 31 pulsotypes using pulsed-field gel electrophoresis, wherein six sequence types belonged to clonal complex 17. Epidemic clones varied throughout the outbreak; however, they all carried vanA -plasmids (pIHVA). pIHVA is a linear plasmid, carrying a unique structural Tn 1546 containing vanA ; it moves between different Enterococcus spp. by genetic rearrangements. VRE infection incidence among patients in the “hot spot” ward correlated with the local VRE colonization prevalence. Local prevalence also correlated with vancomycin usage in the ward. Transmission of a novel transferrable vanA -plasmid among Enterococcus spp. resulted in genomic diversity in VRE in a non-endemic setting. The prevalence of VRE colonization and vancomycin usage at the ward level may serve as VRE cross-transmission indicators in non-intensive care units for outbreak control.