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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.

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.

Vancomycin-resistant enterococci (VRE) are both of medical and public health importance associated with serious multidrug-resistant infections and persistent colonization. Enterococci are opportunistic environmental inhabitants with a remarkable adaptive capacity to evolve and transmit antimicrobial-resistant determinants. The VRE gene operons show distinct genetic variability and apparently continued evolution leading to a variety of antimicrobial resistance phenotypes and various environmental and livestock reservoirs for the most common van genes. Such complex diversity renders a number of important therapeutic options including “last resort antibiotics” ineffective and poses a particular challenge for clinical management. Enterococci resistance to glycopeptides and multidrug resistance warrants attention and continuous monitoring.

In this randomized trial of fidaxomicin as compared with vancomycin in 629 patients, oral fidaxomicin was shown to be noninferior to oral vancomycin in the treatment of C. difficile infection and was associated with lower rates of recurrence. Clostridium difficile infection generally occurs after exposure to broad-spectrum antibiotics. The incidence and severity of C. difficile infection are increasing. The increases have been ascribed to the emergence of a hypervirulent C. difficile strain, known variously as North American Pulsed Field type 1 (NAP1), restriction-endonuclease analysis (REA) type BI, or polymerase-chain-reaction ribotype 027 (referred to collectively as the NAP1/BI/027 strain). 1 – 4 Furthermore, the rates of death associated with C. difficile infection are rising, 5 – 7 and the infection is occurring in populations that were previously considered to be at low risk, such as young, healthy persons living in the community and . . .

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.

Background. Fecal transplantation (FT) is a promising treatment for recurrent Clostridium difficile infection (CDI), but its true effectiveness remains unknown. We compared 14 days of oral vancomycin followed by a single FT by enema with oral vancomycin taper (standard of care) in adult patients experiencing acute recurrence of CDI. Methods. In a phase 2/3, single-center, open-label trial, participants from Ontario, Canada, experiencing recurrence of CDI were randomly assigned in a 1:1 ratio to 14 days of oral vancomycin treatment followed by a single 500-mL FT by enema, or a 6-week taper of oral vancomycin. Patients with significant immunocompromise, history of fulminant CDI, or irreversible bleeding disorders were excluded. The primary endpoint was CDI recurrence within 120 days. Microbiota analysis was performed on fecal filtrate from donors and stool samples from FT recipients, as available. Results. The study was terminated at the interim analysis after randomizing 30 patients. Nine of 16 (56.2%) patients who received FT and 5 of 12 (41.7%) in the vancomycin taper group experienced recurrence of CDI, corresponding with symptom resolution in 43.8% and 58.3%, respectively. Fecal microbiota analysis of 3 successful FT recipients demonstrated increased diversity. A futility analysis did not support continuing the study. Adverse events were similar in both groups and uncommon. Conclusions. In patients experiencing an acute episode of recurrent CDI, a single FT by enema was not significantly different from oral vancomycin taper in reducing recurrent CDI. Further research is needed to explore optimal donor selection, FT preparation, route, timing, and number of administrations. Clinical Trials Registration. NCT01226992.

Target-controlled infusion (TCI) could provide a patient-tailored approach for vancomycin dosing. This study aimed to externally evaluate the predictive performance of a previously constructed pharmacokinetic model of vancomycin (Choi model) specifically optimized for TCI administration of vancomycin differing from the existing model, and to assess the feasibility of administering vancomycin via TCI in clinical practice. Additionally, clinical outcomes were exploratively compared between the TCI and intermittent infusion (standard) methods for vancomycin administration. Clinically ill patients were randomly assigned in a 1:1 ratio to either the TCI or standard group. In the TCI group, vancomycin was administered using the Choi model, targeting an initial concentration of 25 mg/L, adjusted to maintain therapeutic levels (20-30 mg/L). The standard group received a loading dose of 25 mg/kg, then 15 mg/kg every 12 hours. Vancomycin concentrations for analysis were obtained from three blood samples per patient at set times, along with routine therapeutic drug monitoring data. Predictive performance was assessed using four parameters: inaccuracy, divergence, bias, and wobble. The occurrence of acute kidney injury (AKI) during and up to 7 days after vancomycin was investigated. The study was terminated early due to challenges in enrolling subjects (TCI: n=12, standard: n=13). Thirty-seven serum concentration measurements from the TCI group were analyzed. Pooled median bias and inaccuracy (95% confidence interval) were -2.7 (-7.3 to 1.9) and 17.0 (13.9 to 20.2), respectively. AKI incidence was similar between groups (TCI: n=0, standard: n=1) in this exploratory analysis, but caution is warranted in interpreting these outcomes as the planned sample size was not met. The predictive performance of the TCI system integrated with the Choi model was suitable for clinical use. Further studies with a large cohort should be performed to determine the clinical effectiveness of vancomycin administered via the TCI method. This study was registered at the Clinical Research Information Service of the Korean National Institute of Health (CRIS, http://cris.nih.go.kr), with registration number KCT0003462, on January 31, 2019).

Locally applied vancomycin is increasingly being used in primary hip and knee arthroplasty to reduce the risk of infection. Despite encouraging initial results, considerable debate remains on the basis of the data currently available. In particular, it has been unclear up to now whether local vancomycin is suitable to further reduce the risk of infection even if the rate of infection is already low (< 1%). In this monocentric retrospective cohort study, all primary total hip and knee arthroplasties performed between 2013 and 2018 were included. After a change in procedure at the hospital, 1 g vancomycin powder was applied intraarticularly before wound closure. The remaining perioperative procedure was constant over the investigation period. The follow-up was one year. The presence of an infection according to the currently valid MSIS criteria was defined as the endpoint. In patients with TKA two infections (0.3%) were observed under vancomycin prophylaxis in contrast to 44 infections (1.3%) in the control group ( p  = 0.033). In patients with THA two infections (0.5%) were observed under vancomycin prophylaxis and 48 infections (1.1%) in the control group without local vancomycin but this difference was statistically not significant. No wound complications requiring revision were observed as a result of the vancomycin. On the basis of the results of this study, intraarticular application of vancomycin powder in total hip and knee arthroplasty may be considered. Prospective randomized studies have to confirm this promising results prior a common recommendation. Level of Evidence III Retrospective cohort study.

Clostridioides difficile infection (CDI) is a significant cause of hospital-acquired diarrhea, leading to high morbidity, recurrence, and healthcare costs. Probiotics like Saccharomyces boulardii show potential as an adjunct therapy to standard CDI treatment, but further trials are needed to confirm their efficacy. This study assessed the efficacy and safety of S. boulardii combined with vancomycin for treating mild to moderate CDI. 120 CDI patients diagnosed with positive stool toxin test were randomly assigned to receive two capsules of 250 mg of S. boulardii or a placebo every 12 h alongside 125 mg of vancomycin every 6 h for 10 days. The primary endpoint was the clinical cure rate, with secondary endpoints including recurrence, global cure rate, and diarrheal outcomes. Clinical cure rates were similar between groups (98.4% vs. 98.3%), but the combination group had a significantly higher global cure rate (96.6% vs. 85.3%, p  = 0.044) and lower recurrence rate (1.7% vs. 13.1%, p  = 0.032). No significant differences were found in diarrheal outcomes, functional ability, or adverse events. No patients discontinued treatment due to intolerance. In conclusion, adding S. boulardii to vancomycin reduced CDI recurrence without affecting functional recovery or increasing adverse events.

The extensive use of vancomycin has given rise to vancomycin-resistant bacterial strains, such as vancomycin-resistant (VRE). We aim to explore potent medical treatments that can inhibit the growth of VRE. Vancomycin-immobilized gold nanoparticles (Au@Van NPs) with polygonal shapes from one-pot reactions were generated within approximately 7 min. The as-prepared Au NPs exhibit not only antibacterial capability but also photothermal competence. The temperature of the sample solution containing the as-prepared Au@Van NPs can be raised by approximately 15°C under irradiation by a near-infrared laser (λ = 808 nm) within 5 min. The required amount of vancomycin on the as-prepared Au@Van NPs combined with near-infrared irradiation for inhibiting VRE is approximately 16-fold lower than that of free-form vancomycin.