Ingrid Maria Cecilia Rubin

Since 2012, Denmark has seen a significant rise in vancomycin-resistant Enterococcus faecium (VREfm) cases, mirroring trends in other countries, though exceptions occurred during the coronavirus disease 2019 (COVID-19) lockdown and between 2022 and 2023. This rise has been accompanied by ongoing changes in the endemic VREfm clones, reflecting the species’ high genetic plasticity. VREfm rapidly acquires plasmids and mobile genetic elements, enriching it with putative virulence markers (PVMs), including surface proteins, pili, and factors encoding biofilm production and adhesion. L. Roer, H. Kaya, A.P. Tedim, C. Novias, et al. (Microbiol Spectr 12:e0372423, 2024, https://doi.org/10.1128/spectrum.03724-23 ) released a database of 27 PVMs for Enterococcus faecium and Enterococcus lactis . In this study, we examined 516 VREfm bloodstream isolates from 2015 to 2023, identifying eight new putative virulence genes added to the database, bringing the total to 35 PVMs. Using whole-genome sequencing (WGS) and single linkage clustering, we identified six dominant VREfm clusters: ST80-CT14 vanA , ST117-CT24 vanA , ST203-CT859 vanA , ST1421-CT1134 vanA , ST117-CT36 vanB , and ST80-CT2406 vanB . We observed significant differences in the distribution of PVMs, particularly in pilin, gene clusters (PGC-1, PGC-2, and PGC-4), genes involved in carbohydrate metabolism (e.g., orf1481 , ccpA ), and biofilm production (e.g., hylEfm , capD , lysM3 ). These differences could explain variability in pathogenicity, metabolism, and adaptation to stress, contributing to shifts in endemic clones. IMPORTANCE: The newly developed and now updated database, VirulenceFinder, features 35 potential virulence markers for E. faecium and E. lactis , is highly scalable and provides a valuable tool for the in-depth analysis of closely related species using whole-genome sequencing (WGS) data. It holds considerable promise for a range of public health applications, such as hospital outbreak investigations, surveillance, and assessment of pathogenicity of bacterial species.

Zika Virus Infection in Pregnant Traveler Returning to Denmark from Phuket, Thailand, 2024

Objectives: The aim of this systematic review was to investigate the effect of antibiotics on the eradication of multidrug-resistant organisms (MRO) in intestinal carriers. We defined multidrug-resistant organisms as vancomycin-resistant Enterococcus faecium (VREfm), and multidrug-resistant Gram-negative Enterobacterales. Methods: We searched the EMBASE, Cochrane Central, and PubMed databases from inception to medio November 2023. We included randomised and controlled clinical trials (RCTs), that investigated the effect of antibiotics on the eradication of multidrug-resistant organisms in intestinal carriers. Finally, we performed a meta-analysis. Results: We included five RTCs in the systematic review. In four studies an effect of antibiotics on the eradication of MRO was shown at the end of intervention, but it was not sustained at follow-up. In the fifth study, the effect at the end of intervention was not reported, and there was no observed effect of the intervention at follow-up. We included four studies in the meta-analysis, and it suggests an effect of antibiotics on the eradication of MRO in intestinal carriers at the end of follow-up with a p-value of 0.04 (95% confidence interval 1.02–1.95). None of the studies reported a significant increase in resistance to the study drug. Gastrointestinal disorders were the most frequent non-severe adverse event. Conclusions: The effect of antibiotics on the eradication of multidrug-resistant organisms in intestinal carriers was not statistically significant in any of the five included studies; however, we found a significant effect in the pooled meta-analysis. As the confidence interval is large, we cannot determine the clinical importance of this finding, and it should be further investigated.

The aim of this review was to assess the efficacy and safety of Lacticaseibacillus rhamnosus GG (LGG) (previously known as Lactobacillus rhamnosus GG) for the eradication of vancomycin-resistant Enterococcus faecium (VREfm) in colonized carriers. We searched Cochrane Central, EMBASE, and the PubMed Library from inception to 21 August 2023, for randomized controlled trials (RCTs) investigating the effectiveness of LGG for the eradication of gastrointestinal carriage of VREfm. An initial screening was performed followed by a full-text evaluation of the papers. Out of 4076 articles in the original screening, six RCTs (167 participants) were included in the review. All were placebo-controlled RCTs. The meta-analysis was inconclusive with regard to the effect of LGG for clearing VREfm colonization. The overall quality of the evidence was low due to inconsistency and the small number of patients in the trials. We found insufficient evidence to support the use of LGG for the eradication of VREfm in colonized carriers. There is a need for larger RCTs with a standardized formulation and dosage of LGG in future trials.

Introduction: The aim of this systematic review of randomized clinical trials (RCTs) was to examine the efficacy, safety, and tolerability of vancomycin for treatment of recurrent Clostridioides difficile infection (rCDI). Methods: The PubMed database was searched from inception to August 23, 2022. An initial screening was performed followed by a full-text evaluation of the papers. Inclusion criteria were RCTs investigating vancomycin for treatment of rCDI. Results: A total of six studies and 269 patients were included in the review. Three studies used a fixed dose regimen of vancomycin, one study used pulse regimen, one study used a taper-and-pulse regimen, and one study used a taper-and-pulse regimen for the participants with two or more recurrences. The resolution of infection varied from 19% to 58.3% in five of six studies reporting this as an outcome. Four out of six studies reported new episodes of rCDI as an intervention outcome, in those studies 50– 63% of participants experienced rCDI. Regarding the safety and tolerability of vancomycin treatment for rCDI, one study described several adverse events regarding gastrointestinal discomfort along with fatigue and skin rash. There were no records of serious adverse events in the included studies. Conclusion: While oral vancomycin is mostly safe and well tolerated in the RCTs reviewed here, the efficacy for treating rCDI varies greatly from 19– 58.3%, and 50– 63% of participants experienced new episodes of rCDI.

The effects of probiotics/synbiotics are seldom investigated in healthy volunteers; therefore, this study is important, especially considering the safety aspects of multiple probiotics together with prebiotic fiber in consumption by humans. The study explores at the potential of a synbiotic intervention with lactobacilli, bifidobacteria, and inulin in healthy volunteers and tracks the ingested probiotic strain B. animalis subsp. lactis .

Whereas other studies exploring the effect of L. rhamnosus in clearing VREfm from the intestine included children and adults, with a wider age range, our study consisted of a geriatric patient cohort. The natural clearance of VREfm in this study was almost 60% after 4 weeks, thus much higher than described previously.

Vancomycin-resistant Enterococcus faecium (VREfm) is a globally significant nosocomial pathogen with a rapidly increasing prevalence. The objectives were to investigate VREfm outbreak duration and study the additional impact that infection control bundle strategies (ICBSs) set up to curb coronavirus disease 2019 (COVID-19) spreading had on VREfm outbreaks. Outbreak data set were collected prospectively from April 2, 2014 to August 13, 2020 at Copenhagen University Hospital Bispebjerg, Denmark. All VREfm samples had polymerase chain reaction performed for vanA / vanB genes before whole genome sequencing using the Illumina MiSeq platform. The relatedness of isolates was studied by core genome multilocus sequence typing (cgMLST) using Ridom SeqSphere. Eighty-one outbreaks had a median outbreak duration of 32.5 days (range 5–204 days) and 1,161 VREfm isolates were sequenced. The same cgMLST cluster types reappeared after outbreaks were terminated. When comparing the first 5 months of the COVID-19 pandemic with the corresponding period in 2019, we found a 10-fold decrease in VREfm outbreak patients and median outbreak duration decreased from 56 to 7 days (88%). Several COVID-19 ICBSs were implemented from March 13 through summer 2020. VREfm outbreaks lasted up to 204 days, but our findings suggest that outbreaks might last longer since the same cgMLST persisted in the same wards for years implying an endemic situation with recurrent outbreaks caused by hospital reservoirs or readmittance of unknown VREfm carriers. The sharp decline in VREfm outbreaks during the COVID-19 pandemic was most likely due to the ICBSs, resulting in a decrease in VREfm transmission.

Background: Since 2012, the incidence of vancomycin-resistant Enterococcus faecium (VREfm) has increased dramatically in Copenhagen and vanA E. faecium has become endemic and polyclonal. Objectives: To examine whether a patient with a positive VRE clinical sample had the same VREfm in a preceding screening sample (within 60days). Methods: We performed a 30month retrospective study. From our laboratory information system (LIS), we identified all patients with an invasive VREfm isolate and a VREfm rectal screening isolate within 60days before infection. VREfm pairs (screening isolate and invasive isolate) were whole-genome sequenced. All isolates were analysed using SeqSphere and core-genome MLST (cgMLST) types were determined. We examined all isolates for the presence of the three most dominant vanA plasmids in the Capital Region of Denmark. Two novel vanA plasmids were closed by Nanopore/Illumina sequencing. Results: We found a total of 19 VREfm pairs. Of these, 13 patients had pairs with matching cgMLST types and vanA plasmids and a median number of 6days from identification of carriage to clinical infection. One patient had a pair with non-matching cgMLST types but matching vanA plasmids and 24days between identification of carriage to clinical infection. Five patients had pairs with non-matching cgMLST types and non-matching vanA plasmids and a median number of 18days from identification of carriage to clinical infection. Conclusions: Of our 19 pairs, 13 were a match regarding cgMLST types (68%) and 1 more (5%) had matching vanA plasmids. Infection was thus preceded by colonization with the same isolates in 13 out of 19 patients. The five mismatches (26%) could be explained by the longer interval between colonization and infection.