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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.

OBJECTIVE To assess clinically relevant outcomes after complete cessation of control measures for vancomycin-resistant enterococci (VRE). DESIGN Quasi-experimental ecological study over 3.5 years. METHODS All VRE screening and isolation practices at 4 large academic hospitals in Ontario, Canada, were stopped on July 1, 2012. In total, 618 anonymized abstracted charts of patients with VRE-positive clinical isolates identified between July 1, 2010, and December 31, 2013, were reviewed to determine whether the case was a true VRE infection, a VRE colonization or contaminant, or a true VRE bacteremia. All deaths within 30 days of the last VRE infection were also reviewed to determine whether the death was fully or partially attributable to VRE. All-cause mortality was evaluated over the study period. Generalized estimating equation methods were used to cluster outcome rates within hospitals, and negative binomial models were created for each outcome. RESULTS The incidence rate ratio (IRR) for VRE infections was 0.59 and the associated P value was .34. For VRE bacteremias, the IRR was 0.54 and P=.38; for all-cause mortality the IRR was 0.70 and P=.66; and for VRE attributable death, the IRR was 0.35 and P=.49. VRE control measures were not significantly associated with any of the outcomes. Rates of all outcomes appeared to increase during the 18-month period after cessation of VRE control measures, but none reached statistical significance. CONCLUSION Clinically significant VRE outcomes remain rare. Cessation of all control measures for VRE had no significant attributable adverse clinical impact. Infect Control Hosp Epidemiol 2016;1-7.

We report the results of a subgroup analysis of the Benefits of Universal Glove and Gown trial. In 20 intensive care units, the reduction in acquisition of methicillin-resistant Staphylococcus aureus observed in this trial was observed in units also using chlorhexidine bathing and in those that previously performed active surveillance. Infect Control Hosp Epidemiol 2015;00(0): 1–4

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 a prospective genomic surveillance study of liver transplant patients, we found that temporal dynamics differed between multidrug-resistant organisms with respect to onset of intestinal colonization, clearance, and infections. Whole-genome sequencing revealed an unexpected diversity of carbapenem-resistant Enterobacteriaceae. Abstract Background Multidrug-resistant organisms (MDROs) are an important cause of morbidity and mortality after solid organ transplantation. We aimed to characterize MDRO colonization dynamics and infection in liver transplant (LT) recipients through innovative use of active surveillance and whole-genome sequencing (WGS). Methods We prospectively enrolled consecutive adult patients undergoing LT from March 2014 to March 2016. Fecal samples were collected at multiple timepoints from time of enrollment to 12 months posttransplant. Samples were screened for carbapenem-resistant Enterobacteriaceae (CRE), Enterobacteriaceae resistant to third-generation cephalosporins (Ceph-RE), and vancomycin-resistant enterococci. We performed WGS of CRE and selected Ceph-RE isolates. We also collected clinical data including demographics, transplant characteristics, and infection data. Results We collected 998 stool samples and 119 rectal swabs from 128 patients. MDRO colonization was detected in 86 (67%) patients at least once and was significantly associated with subsequent MDRO infection (0 vs 19.8%, P = .002). Child-Turcotte-Pugh score at LT and duration of post-LT hospitalization were independent predictors of both MDRO colonization and infection. Temporal dynamics differed between MDROs with respect to onset of colonization, clearance, and infections. We detected an unexpected diversity of CRE colonizing isolates and previously unrecognized transmission that spanned Ceph-RE and CRE phenotypes, as well as a cluster of mcr-1-producing isolates. Conclusions Active surveillance and WGS showed that MDRO colonization is a highly dynamic and complex process after LT. Understanding that complexity is crucial for informing decisions regarding MDRO infection control, use of therapeutic decolonization, and empiric treatment regimens.

Vancomycin-resistant Enterococcus faecium (VREfm) is a major nosocomial pathogen. Identifying VREfm transmission dynamics permits targeted interventions, and while genomics is increasingly being utilised, methods are not yet standardised or optimised for accuracy. We aimed to develop a standardized genomic method for identifying putative VREfm transmission links. Using comprehensive genomic and epidemiological data from a cohort of 308 VREfm infection or colonization cases, we compared multiple approaches for quantifying genetic relatedness. We showed that clustering by core genome multilocus sequence type (cgMLST) was more informative of population structure than traditional MLST. Pairwise genome comparisons using split k-mer analysis (SKA) provided the high-level resolution needed to infer patient-to-patient transmission. The more common mapping to a reference genome was not sufficiently discriminatory, defining more than three times more genomic transmission events than SKA (3729 compared to 1079 events). Here, we show a standardized genomic framework for inferring VREfm transmission that can be the basis for global deployment of VREfm genomics into routine outbreak detection and investigation. Vancomycin-resistant Enterococcus faecium is an important healthcare-associated pathogen and genomic analyses could inform targeted interventions. Here, the authors optimise an analysis pipeline for identification of putative transmission events using core genome multilocus sequence type clustering and split kmer analysis.

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.

Background. Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection (BSI) are limited. Daptomycin, although not currently approved for this indication, is frequently used for the treatment of VRE-BSI. Its optimal dose still needs to be determined. Methods. We conducted a prospective, observational, cohort study during 2010–2015. We included patients who received a daptomycin dose of ≥6 mg/kg for the treatment of VRE-BSI caused by daptomycin-susceptible VRE. The primary endpoint was 14-day mortality, and multivariable logistic regression was performed for outcome analysis. Results. We included 112 patients treated with daptomycin for VRE-BSI and with evaluable clinical outcomes. The daptomycin minimum inhibitory concentration (MIC) was 4 mg/L in 78 (69.6%) and ≤2 mg/L in 34 (30.4%) isolates. The overall mortality was 40/112 (35.7%). The unadjusted mortality was 18/36 (50.0%) for a daptomycin dose of <7 mg/kg, 17/51 (33.3%) for a dose of 7–9 mg/kg, and 5/25 (20%) for a dose of ≥9 mg/kg (P = .05). The best outcomes were associated with a daptomycin dose of ≥9 mg/kg compared to doses of <7 mg/kg (adjusted odds ratio [aOR], 10.57; 95% confidence interval [CI], 2.25–49.62; P=.003) and 7–9 mg/kg (aOR, 5.01; 95% CI, 1.14–21.98; P=.03). There was no significant difference in mortality with respect to the daptomycin MIC. There was no association between daptomycin dose and elevated creatinine kinase. Conclusion. Higher daptomycin doses (≥9 mg/kg) were associated with lower mortality in patients with VRE-BSI. Our results suggest that higher daptomycin doses need to be considered for VRE-BSI treatment.

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.