Pharmacokinetic and pharmacodynamic evaluation of nitrofurantoin against Escherichia coli in a murine urinary tract infection model.

The antimicrobial agent nitrofurantoin is becoming increasingly important for treatment of urinary tract infections (UTIs) due to widespread occurrence of multidrug-resistant Escherichia coli. Despite many years of use, little data on nitrofurantoin pharmacokinetics (PK) or -dynamics (PD) exist. The objective of this study was to (i) evaluate the pharmacokinetics of nitrofurantoin in a mouse model and (ii) use that data to design an in vivo dose fractionation study in an experimental model of UTI with E. coli for determination of the most predictive PK/PD index. Nitrofurantoin concentrations in urine were approximately 100-fold larger than concentrations in plasma after oral administration of 5, 10, and 20 mg/kg nitrofurantoin. The area under the curve over the minimum inhibitory concentration (AUC/MIC) was weakly correlated to bacterial reduction in urine (r2 = 0.24), while no such correlation was found for the time that nitrofurantoin stayed above the MIC (T > MIC). Increasing size of single-dose treatment was significantly correlated to eradication of bacteria in the urine, while this was not apparent when the same doses were divided in 2 or 3 doses 8 or 12 h apart. In conclusion, the results indicate that nitrofurantoin activity against E. coli in urine is driven by AUC/MIC.

Apramycin efficacy against carbapenem- and aminoglycoside-resistant Escherichia coli and Klebsiella pneumoniae in murine blood stream infection models.

BACKGROUND: The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, its potential in the treatment of drug-resistant bloodstream infections (BSIs) has yet to be assessed. METHODS: The resistance gene annotations of 40 888 blood culture isolates were analyzed. In vitro profiling of apramycin comprised cell-free translation assays, broth microdilution, and frequency of resistance determination. The efficacy of apramycin was studied in a mouse peritonitis model for nine Escherichia coli and Klebsiella pneumoniae isolates. RESULTS: Genotypic aminoglycoside resistance was identified in 87.8% of all 6973 carbapenem-resistant Enterobacterales blood-culture isolates, in comparison to 46.4% of colistin and 2.1% of apramycin resistance. Apramycin activity against methylated ribosomes was > 100-fold higher than other aminoglycosides. Frequencies of resistance were < 10-9 at 8  ×  MIC. Tentative epidemiological cutoffs (ECOFFs) were determined as 8 µg/mL for E. coli and 4 µg/mL for K. pneumoniae. A single dose of 5 to 13 mg/kg resulted in a 1-log CFU reduction in the blood and peritoneum. Two doses of 80 mg/kg, resulting in an exposure that resembles the AUC observed for a single 30 mg/kg dose in humans, resulted in complete eradication of carbapenem- and aminoglycoside-resistant bacteremias. CONCLUSION: Encouraging coverage and potent in vivo efficacy against a selection of highly drug-resistant Enterobacterales isolates in the mouse peritonitis model warrants further consideration of clinical studies to validate apramycin as a drug candidate for the treatment and prophylaxis of BSI.

Risk of Major Types of Dementias Following Hospital-Diagnosed Infections and Autoimmune Diseases.

Background: Population-based studies have shown an increased risk of dementia after infections, but weaker links were reported for autoimmune diseases. Evidence is scarce for whether the links may be modified by the dementia or exposure subtype. Objective: We aimed to investigate the association between infections and/or autoimmune diseases and rates of major types of dementias in the short- and long terms. Methods: Nationwide nested case-control study of dementia cases (65+ years) diagnosed in Denmark 2016-2020 and dementia-free controls. Exposures were hospital-diagnosed infections and autoimmune diseases in the preceding 35 years. Two groups of dementia cases were those diagnosed in memory clinics (MC) and those diagnosed outside memory clinics (non-memory clinic cases, NMC). Results: In total, 26,738 individuals were MC and 12,534 were NMC cases. Following any infection, the incidence rate ratio (IRR) for MC cases was 1.23 (95% CI 1.20-1.27) and 1.70 for NMC cases (1.62-1.76). Long-term increased rates were seen for vascular dementia and NMC cases. IRRs for autoimmune diseases were overall statistically insignificant. Conclusions: Cases with vascular dementia and not Alzheimer's disease, and a subgroup of cases identified with poorer health have increased long-term risk following infections. Autoimmune diseases were not associated with any type of dementia. Notably increased risks (attributed to the short term) and for NMC cases may indicate that immunosenescence rather than de novo infection explains the links. Future focus on such groups and on the role of vascular pathology will explain the infection-dementia links, especially in the long term.

Hit-to-Lead Identification and Validation of a Triaromatic Pleuromutilin Antibiotic Candidate.

Herein, we report the hit-to-lead identification of a drug-like pleuromutilin conjugate 16, based on a triaromatic hit reported in 2020. The lead arose as the clear candidate from a hit-optimization campaign in which Gram-positive antibacterial activity, solubility, and P-gp affinity were optimized. Conjugate 16 was extensively evaluated for its in vitro ADMET performance which, apart from solubility, was overall on par with lefamulin. This evaluation included Caco-2 cell permeability, plasma protein binding, hERG inhibition, cytotoxicity, metabolism in microsomes and CYP3A4, resistance induction, and time-kill kinetics. Intravenous pharmacokinetics of 16 proved satisfactory in both mice and pigs; however, oral bioavailability was limited likely due to insufficient solubility. The in vivo efficacy was evaluated in mice, systemically infected with Staphylococcus aureus, where 16 showed rapid reduction in blood bacteriaemia. Through our comprehensive studies, lead 16 has emerged as a highly promising and safe antibiotic candidate for the treatment of Gram-positive bacterial infections.

Treating urinary tract infections in the era of antibiotic resistance.

INTRODUCTION: Urinary tract infections (UTIs) are associated with 25-40% of antibiotics consumed in primary care and are, therefore, driving antibiotic resistance. The worldwide increase in antibiotic resistance especially in Escherichia coli has complicated the treatment choices for UTIs and absence of effective oral antibiotics may lead to increasing need for more effective treatments. AREAS COVERED: In this review we focus on the importance of the correct diagnosis of UTI as based on proof of urinary pathogens in the urine and discuss diagnostic measures including microscopy, dipstick, and culture. Antibiotic treatment can often await diagnostic measures with pain relief such as ibuprofen. The risk of an uncomplicated UTI leading to pyelonephritis is low (1-2%) and presence of bacteria in the bladder leaves some time for the immune system to react. Three antibiotics are recommended as based on their activity, and low propensity to select for resistance, i.e. nitrofurantoin, fosfomycin, and pivmecillinam, and in general, 3-5 days of treatment will suffice. EXPERT OPINION: Understanding the usual benign course of uUTIs can help reduce antibiotic treatment in many cases, e.g. starting treatment by pain relief and awaiting the course of infection without antibiotics. Better rapid tests in primary care are urgently needed to enforce such policies.

Hospital-Diagnosed Infections, Autoimmune Diseases, and Subsequent Dementia Incidence.

Importance: Systemic inflammation has been suggested to explain reported associations between infections and dementia. Associations between autoimmune diseases and dementia also suggest a role for peripheral systemic inflammation. Objective: To investigate the associations of infections and autoimmune diseases with subsequent dementia incidence and to explore potential shared signals presented by the immune system in the 2 conditions. Design, Setting, and Participants: This nationwide, population-based, registry-based cohort study was conducted between 1978 and 2018 (40-year study period). All Danish residents born 1928 to 1953, alive and in Denmark on January 1, 1978, and at age 65 years were included. Persons with prior registered dementia and those with HIV infections were excluded. Data were analyzed between May 2022 and January 2023. Exposures: Hospital-diagnosed infections and autoimmune diseases. Main Outcomes and Measures: All-cause dementia, defined as the date of a first registered dementia diagnosis after age 65 years in the registries. Poisson regression with person-years at risk as an offset variable was used to analyze time to first dementia diagnosis. Results: A total of 1 493 896 individuals (763 987 women [51%]) were followed for 14 093 303 person-years (677 147 [45%] with infections, 127 721 [9%] with autoimmune diseases, and 75 543 [5%] with dementia). Among individuals with infections, 343 504 (51%) were men, whereas among those with autoimmune diseases, 77 466 (61%) were women. The dementia incidence rate ratio (IRR) following any infection was 1.49 (95% CI, 1.47-1.52) and increased along with increasing numbers of infections in a dose-dependent manner. Dementia rates were increased for all infection sites in the short term, but not always in the long term. The dementia IRR following any autoimmune disease was 1.04 (95% CI, 1.01-1.06), but no dose-dependent increase was observed, and only a few autoimmune conditions showed increased IRRs for dementia. Conclusions and Relevance: These findings may point toward a role for infection-specific processes in the development of dementia, rather than general systemic inflammation, as previously hypothesized. Assessing these 2 conditions in a single setting may allow for additional insights into their roles in dementia and for hypotheses on possible underlying mechanisms.

Dogs Can Be Reservoirs of Escherichia coli Strains Causing Urinary Tract Infection in Human Household Contacts.

This study aimed to investigate the role played by pets as reservoirs of Escherichia coli strains causing human urinary tract infections (UTIs) in household contacts. Among 119 patients with community-acquired E. coli UTIs, we recruited 19 patients who lived with a dog or a cat. Fecal swabs from the household pet(s) were screened by antimicrobial selective culture to detect E. coli displaying the resistance profile of the human strain causing UTI. Two dogs shed E. coli isolates indistinguishable from the UTI strain by pulsed-field gel electrophoresis. Ten months later, new feces from these dogs and their owners were screened selectively and quantitatively for the presence of the UTI strain, followed by core-genome phylogenetic analysis of all isolates. In one pair, the resistance phenotype of the UTI strain occurred more frequently in human (108 CFU/g) than in canine feces (104 CFU/g), and human fecal isolates were more similar (2-7 SNPs) to the UTI strain than canine isolates (83-86 SNPs). In the other pair, isolates genetically related to the UTI strain (23-40 SNPs) were only detected in canine feces (105 CFU/g). These results show that dogs can be long-term carriers of E. coli strains causing UTIs in human household contacts.

Switch from intravenous-to-oral antibiotics in neonatal probable and proven early-onset infection: a prospective population-based real-life multicentre cohort study.

OBJECTIVE: To evaluate the implementation of switch from intravenous-to-oral antibiotic therapy with amoxicillin in neonates with early-onset infection (EOI). DESIGN, SETTING AND PATIENTS: A population-based multicentre cohort study. All term-born neonates with EOI were prospectively included between 1 December 2018 to 30 November 2020. INTERVENTION: Intravenous-to-oral switch antibiotic therapy in clinically stable neonates. MAIN OUTCOME MEASURES: The primary outcome was readmission due to infection. Secondary outcomes were days of hospitalisation and antibiotic use in the pre-implementation versus post implementation period. RESULTS: During 2 years, 835 neonates commenced antibiotics for EOI (1.5% (95% CI 1.4% to 1.6%)) of all term live births). Of those, 554 (66%) underwent a full course of treatment. There were 23 episodes of culture-proven infection (0.42 per 1000 term live births (95% CI 0.27 to 0.63)). A total of 478 of 531 (90%) neonates with probable infection underwent switch therapy. None was readmitted due to infection. The median duration of hospitalisation was 3.0 days (IQR 2.5-3.5) and 7.4 days (IQR 7.0-7.5) in the switch and intravenous therapy groups, respectively. According to antibiotic surveillance data, 1.2% underwent a full course of treatment following implementation of oral switch therapy (2019-2020), compared with 1.2% before (2017-2018). CONCLUSION: In clinical practice, switch therapy was safe and used in 9 of 10 neonates with probable EOI. Knowledge of the safety of antibiotic de-escalation is important as home-based oral therapy ameliorates the treatment burden for neonates, caregivers and healthcare systems. Despite the ease of oral administration, implementation of switch therapy did not increase the overall use of antibiotics.

High level of colonization with third-generation cephalosporin-resistant Enterobacterales in African community settings, Ghana.

A cross-sectional survey was conducted in eight Ghanaian communities to investigate the extent of intestinal colonization with 3rd-generation cephalosporin-resistant Enterobacterales. The study collected faecal samples and corresponding lifestyle data from 736 healthy residents to assess the occurrence of cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae, with a focus on genotypes of plasmid-mediated ESBLs, AmpCs, and carbapenemases. The results showed that 371 participants (50.4%) carried 3rd-generation cephalosporin-resistant E. coli (n=362) and K. pneumoniae (n=9). Most of these were ESBL-producing E. coli (n=352, 94.9%), carrying CTX-M genes (96.0%, n=338/352), mostly for CTX-M-15 (98.9%, n=334/338). Nine participants (1.2%) carried AmpC-producing E. coli that harboured blaDHA-1 or blaCMY-2 genes, and two participants (0.3%) each carried a carbapenem-resistant E. coli that harboured both blaNDM-1 and blaCMY-2. Quinolone-resistant O25b: ST131 E. coli were recovered from six participants (0.8%) and were all CTX-M-15 ESBL-producers. Having a household toilet facility was significantly associated with a reduced risk of intestinal colonization (adjusted odds ratio, 0.71; 95% CI, 0.48-0.99; P-value=0.0095) in multivariate analysis. These findings raise serious public health concerns, and effective control of the spread of antibiotic-resistant bacteria is possible by providing better sanitary conditions for communities.

Invasive procedures and risk of brain abscess: a nationwide, population-based case-control study.

OBJECTIVES: It is unknown whether invasive procedures are associated with brain abscess. METHODS: Nationwide, population-based, matched case-control study of patients with culture verified brain abscess in Denmark from 1989 to 2016. Exposure was invasive procedures 0-6 months before study inclusion. RESULTS: We identified 435 patients and 3909 controls. The level of comorbidity was higher among patients with brain abscess than among controls. A total of 48 cases (11%) had one or more invasive procedures 0-6 months before study inclusion (adjusted odds ratios (aOR) of 3.6 (95% confidence interval (CI): 2.5-5.1), a population attributable fractions of 8% (95% CI: 7-9)). In primary care, ear, nose and throat (ENT) procedures were associated with brain abscess (aOR of 4.0 (95% CI: 2.0-8.0)), but gastrointestinal endoscopies were not (aOR of 1.0 (95% CI: 0.3-3.2)). No bronchoscopies were performed in primary care. In the hospital-based setting, ENT procedures, bronchoscopies and gastrointestinal endoscopies were associated with an increased risk of brain abscess (aOR of 14.5 (95% CI: 4.8-43.8), 20.3 (95% CI: 3.8-110.1) and 3.4 (95% CI: 2.0-5.6), respectively). CONCLUSIONS: The association between invasive procedures and brain abscess was more pronounced in the hospital-based setting than in primary care.

Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication in Patients With Brain Abscess in Denmark.

BACKGROUND: It is unknown whether patients diagnosed with brain abscess have an increased risk of psychiatric disorders. METHODS: In this nationwide, population-based matched cohort study from Denmark, we compared the incidence of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medications between patients diagnosed with brain abscess and individuals from the general population, matched on date of birth, sex, and residential area. RESULTS: We included 435 patients diagnosed with brain abscess and 3909 individuals in the comparison cohort: 61% were male and median age was 54 years. Patients diagnosed with brain abscess were more likely to suffer from comorbidity. The risk of a hospital diagnosis of psychiatric disorders was increased the first 5 years of observation. In the subpopulation, who had never been in contact with psychiatric hospitals or received psychiatric medication before study inclusion, the risk of developing psychiatric disorders was close to that of the background population, especially when we excluded dementia from this outcome. There was a substantial increase in the receipt of anxiolytics and antidepressants. The difference in the proportion of individuals who received anxiolytics and antidepressants increased from 4% (95% confidence interval [CI], 0%-7%) and 2% (95% CI, -1% to 5%) 2 years before study inclusion to 17% (95% CI, 12%-21%) and 11% (95% CI, 7%-16%) in the year after study inclusion. CONCLUSIONS: Patients with brain abscess without prior psychiatric disorders or receipt of psychiatric medicine are not at increased risk psychiatric disorders diagnosed in psychiatric hospitals, but they have an increased receipt of psychiatric medication.

The Risk of Pyelonephritis Following Uncomplicated Cystitis: A Nationwide Primary Healthcare Study.

BACKGROUND: The risk of pyelonephritis following uncomplicated lower urinary tract infection (cystitis) in women has not been studied in well-powered samples. This is likely due to the previous lack of nationwide primary healthcare data. We aimed to examine the risks of pyelonephritis following cystitis in women and explore if antibiotic treatment, cervical cancer, parity, and sociodemographic factors are related to these risks. METHODS: This was a nationwide cohort study (2006-2018) of 752,289 women diagnosed with uncomplicated cystitis in primary healthcare settings. Of these, 404 696 did not redeem an antibiotic prescription within five days from cystitis. Logistic regression models were used to calculate odds ratios for pyelonephritis within 30 days and 90 days following the cystitis event. RESULTS: Around one percent (7454) of all women with cystitis were diagnosed with pyelonephritis within 30 days, of which 78.2% had not redeemed an antibiotic for their cystitis. Antibiotic treatment was inversely associated with both outpatient registration and hospitalization due to pyelonephritis, with odds ratios of 0.85 (95% CI 0.80 to 0.91) and 0.65 (95% CI 0.55 to 0.77), respectively. Sociodemographic factors, parity, and cervical cancer were, with few exceptions (e.g., age and region of residency), not associated with pyelonephritis. CONCLUSIONS: Antibiotic treatment was inversely associated with pyelonephritis, but the absolute risk reduction was low. Non-antibiotic treatment for cystitis might be a safe option for most women. Future studies identifying the women at the highest risks will help clinicians in their decision making when treating cystitis, while keeping the ecological costs of antibiotics in mind.

Pivmecillinam, the paradigm of an antibiotic with low resistance rates in Escherichia coli urine isolates despite high consumption.

OBJECTIVES: Pivmecillinam, the oral version of mecillinam, represents one of the major recommended and used antibiotics for empiric and targeted treatment of urinary tract infections in primary care in Denmark, Norway and Sweden. Mecillinam resistant mutants in Escherichia coli develop easily in vitro, but their fitness cost has been shown to be high. METHODS: We revisited the resistance and consumption data from the monitoring programmes in the three countries and compared pivmecillinam with ciprofloxacin from 2010 to 2020. RESULTS: Mecillinam resistance rates in Escherichia coli remained around 6% in Denmark and Norway relative to a constant consumption in Norway of 1.6-1.8 DID (defined daily doses per 1000 inhabitants per day), and even increasing in Denmark from 1.6 to 2.3 DID. In Sweden resistance was significantly lower at 4% related to the lower consumption of 0.5 DID. For ciprofloxacin, resistance rates fluctuated around 6%-12%, highest in Sweden with the highest consumption (0.8-0.6 DID) and lowest in Denmark (0.55-0.35 DID) and Norway (0.7-0.3 DID), although consumption declined significantly in all three countries. CONCLUSIONS: Pivmecillinam is an example of an antibiotic, which easily develops resistance in vitro, but apparently can be used broadly in primary care without increase in resistance rates.

Synergy between Mecillinam and Ceftazidime/Avibactam or Avibactam against Multi-Drug-Resistant Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae.

Background: Carbapenemase-producing Klebsiella pneumoniae and Escherichia coli have become a significant global health challenge. This has created an urgent need for new treatment modalities. We evaluated the efficacy of mecillinam in combination with either avibactam or ceftazidime/avibactam against carbapenemase-producing clinical isolates. Materials and methods: Nineteen MDR clinical isolates of K. pneumoniae and E. coli were selected for the presence of blaKPC, blaNDM, blaOXA or blaIMP based on whole-genome sequencing and phenotypic susceptibility testing. We tested the synergy between mecillinam and avibactam or ceftazidime/avibactam. We used time−kill studies in vitro and a mouse peritonitis/sepsis model to confirm the synergistic effect. We investigated avibactam's impact on mecillinam´s affinity for penicillin-binding proteins with a Bocillin assay, and cell changes with phase-contrast and confocal laser scanning microscopy. Results: Mecillinam combined with ceftazidime/avibactam or avibactam substantially reduced MICs (from up to >256 µg/mL to <0.0016 µg/mL) for 17/18 strains. Significant log-CFU reductions were confirmed in time−kill and in vivo experiments. The Bocillin assay did not reveal changes. Conclusion: Mecillinam in combination with avibactam or ceftazidime/avibactam has a notable effect on most types of CPEs, both in vitro and in vivo. The mecillinam/avibactam combination treatment could be a new efficient antibiotic treatment against multi-drug-resistant carbapenemase-producing Gram-negative pathogens.

Isothermal microcalorimetry vs checkerboard assay to evaluate in-vitro synergism of meropenem-amikacin and meropenem-colistin combinations against multi-drug-resistant Gram-negative pathogens.

OBJECTIVES: To evaluate the activity of meropenem-amikacin and meropenem-colistin combinations with checkerboard broth microdilution (CKBM) compared with isothermal microcalorimetry (ITMC) assays against a multi-centric collection of multi-drug-resistant Gram-negative clinical isolates; and to compare the fractional inhibitory concentration (FIC) index and time to results of CKBM and ITMC. METHODS: A collection of 333 multi-drug-resistant Gram-negative clinical isolates showing reduced susceptibility to meropenem (121 Klebsiella pneumoniae, 14 Escherichia coli, 130 Pseudomonas aeruginosa and 68 Acinetobacter baumannii) isolated from different centres (Florence, Madrid, Rotterdam and Stockholm) was included in the study. The antimicrobial activity of meropenem-amikacin and meropenem-colistin combinations was evaluated with CKBM and ITMC. FIC index results were interpreted as synergistic/additive and indifferent for values ≤0.5/0.51, respectively. Whole-genome sequencing data of a subset of strains were used to evaluate their clonality. RESULTS: In total, 254 and 286 strains were tested with meropenem-colistin and meropenem-amikacin combinations with ITMC and CKBM, respectively. Synergistic/additive effects were observed for 46 strains (20 K. pneumoniae, four E. coli, 22 P. aeruginosa) and 20 strains (three K. pneumoniae, 11 P. aeruginosa and six A. baumannii) with meropenem-amikacin and meropenem-colistin combinations, respectively, with CKBM. ITMC showed good concordance with CKBM, with 89.5% and 92.2% of cases interpreted within the same FIC index category for meropenem-amikacin and meropenem-colistin combinations, respectively. Most of the synergistic/additive effects were detected within 6 h by ITMC. CONCLUSIONS: ITMC showed very good concordance with CKBM against a large collection of multi-drug-resistant Gram-negative clinical isolates, and could be implemented for the rapid evaluation of in-vitro activity of antimicrobial combinations.

Vaginal microbiome following orally administered probiotic.

Here, we present a longitudinal shotgun sequencing metagenomics study of 16 healthy, Danish women in the reproductive age. The aim of the study was to investigate whether lactobacilli, orally consumed, had any impact on the vaginal microbiome and its functional potential. The 16 women aged 19-45 years were recruited from Copenhagen, Denmark. One baseline vaginal sample (Day 0) and two study samples (Days 25-30 and Days 55-60, respectively), were sampled. The vaginal samples were analyzed by shotgun metagenomics. We detected 26 species in the vaginal microbiota of the 16 women, of which six belonged to the Lactobacillus genus. We observed three vaginal microbiome clusters mainly dominated by Gardnerella vaginalis, Lactobacillus iners, or Lactobacillus crispatus. The oral probiotic had no detectable effect on either the composition or the functional potential of the vaginal microbiota. Most of the study subjects (11 out of 16 women) exhibited only minor changes in the vaginal microbiome during the treatment with probiotics. Any compositional changes could not be associated to the probiotic treatment. Future studies may benefit from an increased number of participants, and administration of the probiotics during conditions with bacterial imbalance (e.g., during/after antibiotic treatment) or the use of different Lactobacillus spp. known to colonize the vagina.

Vancomycin-resistant Enterococcus faecium: should we screen on admission?

Denmark has experienced an increase in the proportion of invasive vancomycin-resistant Enterococcus faecium (VRE) since 2002 (e.g. <4% in 2015, 7.1% in 2017 and 12% in 2018). At Rigshospitalet, we employ active screening at departments with high prevalence or in case of outbreaks. This includes the collection of rectal swabs specifically for VRE screening. Our purpose was to describe the carrier prevalence of vancomycin-resistant enterococci among acute patients admitted to the Neurointensive Care Unit, Department of Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark (NICU). Between April 2018 and January 2019, we investigated 99 consecutive rectal swabs from patients admitted to NICU. The primary outcome was prevalence of VRE carriage. The median age was 64 years (range 23-87) and gender was equally distributed (Female = 47, Male = 46). 26 (28%) had previously been admitted within 179 days and 67 patients (72%) had no hospital admissions within 180 days prior to the admission to NICU. Of the 93 rectal swabs, 2 (2%, 95% CI 0.26-7.55%) were positive for vanA and none were positive for vanB. Routine screening of all patients at admission may be effective in hospital settings with high VRE prevalence, whereas the benefit of screening for VRE in hospitals with a low prevalence may be restricted to specific patient populations.