Vancomycin-resistant Enterococcus Faecium Research Articles

Analysis of a persistent outbreak with vancomycin resistant Enterococcus faecium (VREfm) revealed the need for an adapted diagnostic algorithm

Analysis of a persistent outbreak with vancomycin resistant Enterococcus faecium (VREfm) revealed the need for an adapted diagnostic algorithm

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin.

Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health1. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action2, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease3, causes cross-resistance to daptomycin in VREfm. Amino acid changes arising within the bacterial RNA polymerase in response to rifaximin exposure cause upregulation of a previously uncharacterized operon (prdRAB) that leads to cell membrane remodelling and cross-resistance to daptomycin through reduced binding of the antibiotic. VREfm with these mutations are spread globally, making this a major mechanism of resistance. Rifaximin has been considered 'low risk' for the development of antibiotic resistance. Our study shows that this assumption is flawed and that widespread rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin, a major last-resort intervention for multidrug-resistant pathogens. These findings demonstrate how unanticipated antibiotic cross-resistance can undermine global strategies designed to preserve the clinical use of critical antibiotics.

Vascular Graft Impregnation with a Fosfomycin/Oritavancin Combination to Prevent Early Infection

Background/Objectives: Vascular graft infections (VGIs) represent a life-threatening complication, occurring in 0.2–6% of patients following aortic prosthetic placements. Historically, the primary focus for reducing VGIs has been on prevention. Currently, antimicrobial grafts are not available on the market. This study aimed to evaluate the efficacy of combining two antibiotics, fosfomycin and oritavancin, impregnated into the commercially available GelweaveTM vascular graft as a prophylactic alternative against the most commonly implicated bacteria responsible for VGI. Methods: The antimicrobial activity of fosfomycin and oritavancin was assessed using the broth microdilution method, and a synergistic effect was demonstrated using the checkerboard assay against Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. The antibiotics were impregnated into the commercial vascular graft through immersion, and the antimicrobial efficacy of the fosfomycin/oritavancin-impregnated graft was assessed over a period of 7 days. Results: Eradication of all microorganisms tested was achieved using impregnation solutions with concentrations of 40 mg/mL of fosfomycin and 256 µg/mL of oritavancin. Conclusions: Impregnation with the combination of fosfomycin/oritavancin proved to be a promising approach to prevent VGIs. Vascular grafts with impregnated antibiotics are not yet available on the market, and this work represents an important step toward the development of a new class of antimicrobial vascular grafts.

Coexistence of seven different carbapenemase producers in a single hospital admission screening confirmed by whole-genome sequencing

ObjectiveTo molecularly characterize several extensively drug-resistant isolates from a single hospital admission screening of a war injured patient from the Ukraine. MethodsAdmission screening included swabs from skin, wounds, catheters, nasopharyngeum and rectum. Bacterial identification, antimicrobial susceptibility testing (AST) and rapid multiplex PCR assays targeting resistance genes were performed during routine diagnostics. Isolates positive by PCR had their genomes sequenced using short- and long read-platforms (MiSeq and MinION) to confirm species, identify resistance genes and plasmids and investigate clonality with core genome MLST (cgMLST). ResultsSeven Gram-negative pathogens (Acinetobacter baumannii (n=2; ST78, ST2), Klebsiella pneumoniae (n=2; ST395), Pseudomonas aeruginosa (n=1; ST1047), Escherichia coli (n=1; ST46), Enterobacter cloacae complex (n=1; ST231)) were molecularly confirmed non-identical. AST showed resistance to carbapenems (7/7 isolates) and last resort treatment options such as ceftazidime-avibactam (6/7 isolates) and cefiderocol (4/7 isolates). All isolates were colistin susceptible. Sequencing identified the E. cloacae complex as E. hormaechei subsp. xiangfangensis. Six acquired carbapenemase genes (blaIMP-1, blaNDM-1, blaOXA-48, blaNDM-5, blaOXA-23 and blaOXA-72) were detected. Both A. baumannii isolates differed in sequence type, carbapenemases and cefiderocol susceptibility. Both K. pneumoniae isolates shared sequence type and some resistance genes on an IncR plasmid but were different in cgMLST and carbapenemases (OXA-48 or NDM-1). One vancomycin-resistant Enterococcus faecium was also detected (VanA). ConclusionWar injured patients from Ukraine may carry different clones of multidrug-resistant pathogens with limited treatment options and diverse resistance genes at risk for dissemination. Infection control measures should include early molecular characterization of isolates for detection of routes of transmission.

Management of vancomycin-resistant Enterococcus faecium in Dutch health care institutes: a nation-wide survey

Vancomycin-resistant Enterococcus faecium (VREfm) is an opportunistic pathogen, which can cause outbreaks in hospitals. In the Netherlands, several national guidelines and guidance documents on different aspects of VREfm-management are available. Most available guidelines are written towards the hospital setting and only few on long-term care facilities (LTCFs). Moreover, not all aspects of VREfm-management are covered, recommendations differ and the level of compliance to these guidelines is unknown. The aim of this study was to get insight into the routine VREfm-policies in Dutch healthcare facilities with regard to screening, diagnostics and infection control measures. Online questionnaires were sent to representatives of Dutch hospitals and long-term care facilities (LTCFs). The questionnaire included questions regarding the definition of VRE, screening, diagnostics, patient isolation, cleaning procedures, VREfm-clearance and VREfm-outbreaks. The questionnaire was completed by 61 hospitals with a response rate of 84.1% and 57 LTCFs, mostly nursing homes. Most hospitals reported VRE-outbreaks in the previous decade, whereas only one LTCFs reported an outbreak. Of the hospitals, 87% perform VREfm-screening versus 50% of the LTCFs. VRE-positive patients are isolated in 98% of hospitals and 83% of LTCFs. Protocols regarding how to unlabel VRE-positive patients are in place in 84% of the hospitals and in 51% of LTCFs. The details of these measures differ substantially between healthcare facilities. This study has shown that most hospitals and some LTCFs in the Netherlands have standard procedures for VREfm-management to some level, although the comprehensiveness and details of the measures differ per hospital. More uniform policies would improve comparability of VREfm data on a regional/national level.

Cumulative incidence of vancomycin-resistant Enterococcus faecium detection by patient characteristics or possible exposures: prioritization of patients for active screening culture

The target population for active surveillance culture (ASC) of vancomycin-resistant Enterococcus species (VRE) by stool or rectal swabs has not been fully determined during VRE outbreaks in healthcare settings in non-VRE endemic situation. We evaluated cumulative incidences of VRE detection during a vancomycin-resistant Enterococcus faecium outbreak to determine reasonable target populations for ASC. Cases included inpatients whose first VRE-positive sample was obtained at Shizuoka General Hospital between February 2022 and January 2023, during which we conducted admission screening for possible high-risk patients, biweekly screening of all inpatients, admission and discharge screening in the high-care unit, and screening of contacts in each ward by using stool or rectal samples. We calculated cumulative incidences of VRE detection for those screened by patient characteristics or possible exposure. Among 60 cases identified, 55 (92%) were by ASC. Cumulative incidence was higher for contacts (6.4%, 15/234) than for those identified by other screening methods (0.5%, 40/8565). Among the patients identified through admission screening, those previously hospitalized in areas of reported VRE outbreaks had the highest cumulative incidence (6.6%, 5/78) followed by patients requiring toilet assistance (3.7%, 6/161). A bundle approach including ASC and prompt contact precautions by the hospital infection control team, local public health centre, and local and national infection control experts helped terminate the outbreak in seven months. Patients with contacts, prior hospitalization in areas with known VRE outbreaks, and who need toilet assistance appear to be high-risk populations for VRE detection and are candidates for ASC.

Potential Use of Fourier-Transform Infrared Spectroscopy as a Rapid Screening Tool for Investigating Nosocomial Outbreaks of ST-80 Vancomycin-Resistant Enterococcus faecium

Core genome single-nucleotide polymorphism phylogeny was used to characterise a nosocomial outbreak caused by ST-80 Vancomycin-resistant Enterococcus faecium (VREf). It identified 22 of 25 epidemiologically related isolates as belonging to an outbreak cluster. The use of Fourier-transform infrared (FT-IR) spectroscopy with a cluster-defining cut-off of 0.071 resulted in the correct classification of 21 of 22 phylogenetically related isolates in a single cluster. It successfully distinguished three phylogenetically unrelated isolates from the outbreak cluster, along with five ST-80 unrelated control isolates, and five isolates from a previous outbreak in May 2023, yielding only one mischaracterised environmental isolate. These findings support the potential use of FT-IR spectroscopy as a rapid screening tool to assist outbreak investigations. Notably, this study is the first to focus on the performance of FT-IR spectroscopy in the epidemiological analysis of VREf isolates with the same sequence type.

SHIN-2 exerts potent activity against VanA-type vancomycin-resistant Enterococcus faecium in vitro by stabilizing the active site loop of serine hydroxymethyltransferase

Novel classes of antibiotics are needed to improve the resilience of the healthcare system to antimicrobial resistance (AMR), including vancomycin resistance. vanA gene cluster is a cause of vancomycin resistance. This gene cluster is transferred and spreads vancomycin resistance from Enterococcus spp. to Staphylococcus aureus. Therefore, novel antibacterial agents are required to combat AMR, including vanA-type vancomycin resistance. Serine hydroxymethyltransferase (SHMT) is a key target of antibacterial agents. However, the specific binding mechanisms of SHMT inhibitors remain unclear. Detailed structural information will contribute to understanding these mechanisms. In this study, we found that (+)–SHIN–2, the first in vivo active inhibitor of human SHMT, is strongly bound to the Enterococcus faecium SHMT (efmSHMT). Comparison of the crystal structures of apo- and (+)–SHIN–2-boud efmSHMT revealed that (+)–SHIN–2 stabilized the active site loop of efmSHMT via hydrogen bonds, which are critical for efmSHMT inhibition. Additionally, (+)–SHIN–2 formed hydrogen bonds with serine, forming the Schiff's base with pyridoxal 5′-phosphate, which is a co-factor of SHMT. Furthermore, (+)–SHIN–2 exerted biostatic effects on vancomycin-susceptible and vanA-type vancomycin-resistant E. faecium in vitro, indicating that SHMT inhibitors do not induce cross-resistance to vanA-type vancomycin. Overall, these findings can aid in the design of novel SHMT inhibitors to combat AMR, including vancomycin resistance.

Identification of Antimicrobial-Resistant Zoonotic Bacteria in Swine Production: Implications from the One Health Perspective.

Antimicrobial resistance poses a major threat to global health and food security and is primarily driven by antimicrobial use in human and veterinary medicine. Understanding its epidemiology at farm level is crucial for effective control measures. Despite the significant reduction in antibiotic use in conventional livestock production, the swine sector traditionally has a higher level of antibiotic use in veterinary medicine. Consequently, multidrug resistance (MDR) among microbial isolates of swine origin has been relatively frequent. The aim of this study was to assess the presence of multidrug-resistant (MDR) bacteria, enteric pathogens and resistance genes to the main antibiotics used in clinical practice, both within the environment and in animals across pig farms characterized by varying degrees of sanitary status. A total of 274 samples were collected. Of these, 34 samples were collected from the environment (wall swabs, slat swabs and slurry pit), and 240 samples were collected from animals (sows' and piglets' rectal faeces). All samples were analysed for MDR bacteria and enteric pathogens. The study revealed a high frequency of extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales and Campylobacter spp., with ESBL-producing Enterobacterales predominating in high health status farms (environment and animals) and Campylobacter spp. in both high health status and low health status environments. Additionally, a high percentage of methicillin-resistant Staphylococcus aureus (MRSA) was found, mainly in environmental samples from high health status farms, and Clostridioides difficile was distributed ubiquitously among farms and samples. Furthermore, though less frequently, vancomycin-resistant Enterococcus faecium (VRE) was isolated only in high health status farms, and Gram-negative bacilli resistant to carbapenems were isolated only in environmental samples of high health status and low health status farms. This study underscores the importance of surveillance for MDR bacteria in farm animals and their environment, including their waste. Such ecosystems serve as crucial reservoirs of bacteria, requiring national-level surveillance to promote responsible antibiotic use and pandemic control.

Development and application of a rapid visual detection technique for VanA gene in vancomycin-resistant Enterococcus faecium.

One of the key approaches to treating and controlling vancomycin-resistant Enterococcus faecium (VREFm) is an accurate and rapid diagnosis. To achieve this goal, a simple and rapid method must be constructed for immediate detection in the field. Multienzyme isothermal rapid amplification (MIRA) is an isothermal rapid amplification method that allows amplification reactions to be completed under room temperature conditions. When combined with lateral flow strips (LFSs), MIRA-LFS enables the rapid detection of pathogenic microorganisms. However, the MIRA method often produces false signals. These false signals are eliminated by using base mismatches introduced in primers and probes. The MIRA-LFS system was constructed with high specificity and sensitivity for the detection of VREfm, without the limitation of sophisticated instruments. This enables the prompt formulation of diagnostic and therapeutic decisions.

Pheno- and Genotypic Epidemiological Characterization of Vancomycin-Resistant Enterococcus faecium Isolates from Intensive Care Unit Patients in Central Türkiye.

Vancomycin-resistant Enterococcus faecium (VRE) has been detected in Türkiye. Only limited information is available on its dissemination in the central regions of the country. This study describes the first epidemiological characterization of VRE clinical isolates detected in patients in a hospital in the province of Aksaray. In this one-year study conducted between 2021 and 2022, stool samples from intensive care unit patients were screened for VRE using the phenotypic E-test method, and the antibiotic sensitivity test was analyzed by using the VITEK® 2 system. A molecular assay for confirmation of species level was carried out by 16S rRNA gene-based sequencing and testing for antibiotic resistance (vanA or vanB) and virulence factor-encoding genes (esp, asa1, and hyl). Further, genotypic characterization was determined by macro-restriction fragment pattern analysis (MRFPA) of genomic DNA digested with SmaI restriction enzyme. Of the total 350 Enterococcus positive patients from different hospital intensive care units, 22 (6.3%) were positive for VRE using the phenotypic E-test method. All isolates showed resistance to ampicillin, ciprofloxacin, vancomycin, and teicoplanin and positive amplification for the vanA gene. However, none of the isolates was positive for the vanB gene. The most prevalent virulence gene was esp. The results indicate that the isolates are persistent in the hospital environment and subsequently transmitted to hospitalized patients, thus representing challenges to an outbreak and infection control. These study results would also help formulate more effective strategies to reduce the transmission and propagation of VRE contamination in various hospital settings.

Emergence of Virulent Extensively Drug-Resistant Vancomycin-Resistant Enterococci Among Diarrheic Pet Animals: A Possible Public Health Threat on the Move.

Background: Vancomycin-resistant enterococci (VRE) have become an increasing public health concern in the past few decades, being associated with serious multidrug-resistant (MDR) infections. This study was conducted to investigate the role of diarrheic pet animals as potential reservoirs for virulent extensively drug-resistant (XDR) VRE and their threat on human health. Materials and Methods: Rectal swabs were collected from 153 diarrheic pet animals (80 dogs and 73 cats). The collected swabs were cultured on CHROMagarTMVRE for the isolation of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, and then suspected colonies were identified as enterococci after Gram staining, conventional biochemical tests, and molecular techniques. VRE were basically identified using the disk diffusion method; however, molecular identification of vanA and vanB genes was carried out among confirmed VRE isolates. Moreover, three virulence genes (cytolysin A, cylA; enterococcal surface protein, esp; and hyaluronidase, hyl) were investigated in VRE isolates. Thereafter, VRE strains that harbored virulence genes were tested for antimicrobial susceptibility. Results: Eighteen out of 153 animals (11.8%) were positive for VRE, which were obtained from 15% and 8.2% of the examined dogs and cats, respectively. None of the obtained isolates carried the vanA gene, whereas the vanB gene was detected in E. faecalis (4/10) with a prevalence rate (40%). Of the obtained VRE isolates, five possessed esp and/or cylA, while all strains were negative for the hyl gene. Furthermore, four virulent VRE isolates exhibited an XDR pattern, and one isolate was MDR. Conclusion: Diarrheic pet animals could represent a potential zoonotic reservoir for virulent XDR vancomycin-resistant E. faecalis, which may have serious public health implications.

Genetic characterization of vancomycin-resistant Enterococcus faecium isolates from neutropenic patients in Tunisia: spread of the pandemic CC17 clone associated with high genetic diversity in Tn1546-like structures.

In Tunisia, limited research has focused on characterizing clinical vancomycin-resistant Enterococcus faecium (VREfm). This study aimed to bridge this knowledge gap by molecular characterization of antimicrobial resistance, determining the genetic elements mediating vancomycin-resistance, and whole-genome sequencing of one representative VREfm isolate. Over 6 years (2011-2016), a total of eighty VREfm isolates responsible for infection or colonization were identified from hospitalized patients, with the incidence rate increasing from 2% in 2011 to 27% in 2016. All of these strains harbored the vanA gene. The screening for antimicrobial resistance genes revealed the predominance of ermB, tetM, and aac(6')-Ie-aph(2'')-Ia genes and 81.2% of strains harbored the Tn1545. Pulsed-field gel electrophoresis identified seven clusters, with two major clusters (belonging to ST117 and ST80) persisting throughout the study period. Seven Tn1546 types were detected, with type VI (truncated transposon) being the most prevalent (57.5%). Whole-genome sequencing revealed a 3 028 373bp chromosome and five plasmids. Mobile genetic elements and a type I CRISPR-cas locus were identified. Notably, the vanA gene was carried by the classic Tn1546 transposon with ISL3 insertion on a rep17pRUM plasmid. A concerning trend in the prevalence of VREfm essentially attributed to CC17 persistence and to horizontal transfer of multiple genetic variants of truncated vanA-Tn1546.

High prevalence of the recently identified clonal lineage ST1299/CT3109 vanA among vancomycin-resistant Enterococcus faecium strains isolated from municipal wastewater.

Previously, we demonstrated that the majority of vancomycin-resistant Enterococcus faecium (VREfm) strains from in-patients of the University Hospital Erlangen, Germany, belonged to only three clonal lineages, namely ST117/CT71 vanB and two novel ST1299 vanA lineages classified as CT3109 and CT1903. The goal of the current study was (i) to investigate whether VREfm is also detectable in wastewater of the city of Erlangen, (ii) to identify their molecular features, and (iii) to clarify whether VREfm could arise from the community of the city of Erlangen or can be (directly) connected to nosocomial infections in the hospital setting. From April to May 2023, a total of 244 VREfm strains from raw wastewater of the city of Erlangen were analyzed by core genome multilocus sequence typing (cgMLST). Moreover, 20 of them were further investigated for single nucleotide polymorphisms (SNPs). The molecular characterization of the wastewater VREfm strains revealed a high prevalence (27.9%) of the recently identified clonal lineage ST1299/CT3109 vanA, which is mainly characterized by the presence of the tetracycline-resistance determinant tet(M) and the virulence genes pilA and prpA. The SNPs analysis revealed the presence of two major clusters, namely cluster I (≤65 SNPs), which included well-known hospital-adapted vanB clonal lineages such as ST117/CT71 and ST80/CT1065 and cluster II (≤70 SNPs), which were mainly characterized by the lineage ST1299/CT3109 vanA. Based on the concomitant resistance to vancomycin and tetracycline, we propose that ST1299/CT3109 vanA primarily originated and spread outside of hospital settings.IMPORTANCEThis study provides a detailed genomic analysis of vancomycin-resistant Enterococcus faecium (VREfm) strains isolated from municipal wastewater with a particular focus on clonal lineages, antimicrobial resistance, and the presence of virulence genes. The high wastewater prevalence of the recently identified clonal lineage ST1299/CT3109 vanA, which has been previously detected in hospitals, suggests an enormous potential for future spread in Germany.

A rationally designed antigen elicits protective antibodies against multiple nosocomial Gram-positive pathogens

SummaryESKAPE pathogens are responsible for complicated nosocomial infections worldwide and are often resistant to commonly used antibiotics in clinical settings. Among ESKAPE, vancomycin-resistant Enterococcus faecium (VREfm) and methicillin-resistant Staphylococcus aureus (MRSA) are two important Gram-positive pathogens for which non-antibiotic alternatives are urgently needed. We previously showed that the lipoprotein AdcA of E. faecium elicits opsonic and protective antibodies against E. faecium and E. faecalis. Prompted by our observation, reported here, that AdcA also elicits opsonic antibodies against MRSA and other clinically relevant Gram-positive pathogens, we identified the dominant epitope responsible for AdcA cross-reactive activity and designed a hyper-thermostable and multi-presenting antigen, Sc(EH)3. We demonstrate that antibodies raised against Sc(EH)3 mediate opsonic killing of a wide-spectrum of Gram-positive pathogens, including VREfm and MRSA, and confer protection both in passive and active immunisation models. Our data indicate that Sc(EH)3 is a promising antigen for the development of vaccines against different Gram-positive pathogens.

Self-Assembling and Pore-Forming Peptoids as Antimicrobial Biomaterials.

Bacterial infections have been a serious threat to mankind throughout history. Natural antimicrobial peptides (AMPs) and their membrane disruption mechanism have generated immense interest in the design and development of synthetic mimetics that could overcome the intrinsic drawbacks of AMPs, such as their susceptibility to proteolytic degradation and low bioavailability. Herein, by exploiting the self-assembly and pore-forming capabilities of sequence-defined peptoids, we discovered a family of low-molecular weight peptoid antibiotics that exhibit excellent broad-spectrum activity and high selectivity toward a panel of clinically significant Gram-positive and Gram-negative bacterial strains, including vancomycin-resistant Enterococcus faecalis (VREF), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Tuning the peptoid side chain chemistry and structure enabled us to tune the efficacy of antimicrobial activity. Mechanistic studies using transmission electron microscopy (TEM), bacterial membrane depolarization and lysis, and time-kill kinetics assays along with molecular dynamics simulations reveal that these peptoids kill both Gram-positive and Gram-negative bacteria through a membrane disruption mechanism. These robust and biocompatible peptoid-based antibiotics can provide a valuable tool for combating emerging drug resistance.

Early identification of the nosocomial spread of vancomycin-resistant Enterococcus faecium by Fourier-transform infrared spectroscopy and performance comparison with PFGE and WGS

ABSTRACT Early detection of disseminating vancomycin-resistant Enterococcus faecium (VREfm) in ICU wards is crucial for outbreak identification and the implementation of prompt infection control measures. Genotypic methods like pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) are costly and time-consuming, hindering rapid response due to batch dependency. Fourier-transform infrared spectroscopy (FT-IR) offers the potential for real-time outbreak detection and reliable strain typing. We utilized FT-IR to identify clonal VREfm dissemination and compared its performance to PFGE and WGS. Between February through October 2023, an unusually high number of VREfm were recovered at a tertiary hospital in Barcelona. Isolates were examined for antimicrobial susceptibility, carriage of vanA/vanB genes and clonality was also studied using FT-IR, PFGE, and WGS. Routine FT-IR inspections revealed recurring VREfm clustering during the outbreak's initial weeks. In total, 104 isolates were recovered from 75 patients and from multiple wards. However, only one isolate was recovered from an environmental sample, suggesting the absence of environmental reservoirs. An ST80 vancomycin-resistant (vanA) E. faecium strain was the main strain responsible for the outbreak, although a few additional VREfm strains were also identified, all belonging to CC17. PFGE and cgMLST (WGS) yielded identical clustering results to FT-IR, and WGS confirmed vanA/vanB gene carriage in all VREfm isolates. Infection control measures led to a rapid decline in VREfm isolates, with no isolates detected in November. FT-IR spectroscopy offers rapid turnaround times, sensitivity, and reproducibility, comparable to standard typing methods. It proved as an effective tool for monitoring VREfm dissemination and early outbreak detection.

Pre-exposure to peracetic acid followed by UV treatment for deactivating vancomycin-resistant Enterococcus faecalis through intracellular attack

Antimicrobial resistance (AMR) poses a global health threat to aquatic environments and its propagation is a hot topic. Therefore, deactivating antibiotic-resistant bacteria (ARB) and removing antibiotic resistance genes (ARGs) from water is crucial for controlling AMR transmission. Peracetic acid (PAA), which is known for its potent oxidizing properties and limited by-product formation, is emerging as a favorable disinfectant for water treatment. In this study, we aimed to assess the efficacy of pre-exposure to PAA followed by UV treatment (PAA-UV/PAA) compared with the simultaneous application of UV and PAA (UV/PAA). The focus was on deactivating vancomycin-resistant Enterococcus faecalis (VREfs), a typical ARB in water. Pre-exposure to PAA significantly enhanced the efficacy of subsequent UV/PAA treatment. At a UV fluence of 7.2 mJ cm−2, the PAA-UV/PAA method achieved a 6.21 log reduction in VREfs, surpassing the 1.29 log reduction observed with UV/PAA. Moreover, compared to UV/PAA, PAA-UV/PAA showed increased efficacy with longer pre-exposure times and higher PAA concentrations, maintaining superior performance across a broad pH range and in the presence of humic acid. Flow cytometry analysis indicated minimal cellular membrane damage using both methods. However, the assessments of superoxide dismutase (SOD) activity and adenosine triphosphate content revealed that PAA-UV/PAA induced greater oxidative stress under similar UV irradiation conditions, leading to slower bacterial regrowth. Specifically, SOD activity in PAA-UV/PAA surged to 3.06 times its baseline, exceeding the 1.73-fold increase under UV/PAA conditions. Additionally, pre-exposure to PAA amplified ARGs degradation and reduced resistance gene leakage, effectively mitigating the spread of AMR. Pre-exposure to 200 μM PAA for 10 and 20 min enhanced vanB gene removal efficiency by 0.14 log and 1.29 log, respectively. Our study provides a feasible approach for optimizing UV/PAA disinfection for efficient removal of ARB and ARGs.

The Effect of Antibiotics on the Eradication of Multidrug-Resistant Organisms in Intestinal Carriers-A Systematic Review with Meta-Analysis.

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. 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. 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.

Bacteriocin production facilitates nosocomial emergence of vancomycin-resistant Enterococcus faecium.

Vancomycin-resistant Enterococcus faecium (VREfm) is a prevalent healthcare-acquired pathogen. Gastrointestinal colonization can lead to difficult-to-treat bloodstream infections with high mortality rates. Prior studies have investigated VREfm population structure within healthcare centers. However, little is known about how and why hospital-adapted VREfm populations change over time. We sequenced 710 healthcare-associated VREfm clinical isolates from 2017-2022 from a large tertiary care center as part of the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT) program. Although the VREfm population in our center was polyclonal, 46% of isolates formed genetically related clusters, suggesting a high transmission rate. We compared our collection to 15,631 publicly available VREfm genomes spanning 20 years. Our findings describe a drastic shift in lineage replacement within nosocomial VREfm populations at both the local and global level. Functional and genomic analysis revealed, antimicrobial peptide, bacteriocin T8 may be a driving feature of strain emergence and persistence in the hospital setting.