Successful containment of two vancomycin-resistant Enterococcus faecium (VRE) outbreaks in a Dutch teaching hospital using environmental sampling and whole-genome sequencing.

BACKGROUND: Vancomycin-resistant enterococci (VRE) may cause nosocomial outbreaks. This article describes all VRE carriers that were identified in 2018 at Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands. AIM: To investigate the genetic relatedness of VRE isolates and the possibility of a common environmental reservoir using environmental sampling and whole-genome sequencing (WGS). METHODS: Infection control measures consisted of contact isolation, contact surveys, point prevalence screening, environmental sampling, cleaning and disinfection. VRE isolates were sequenced using a MiSeq sequencer (Illumina, San Diego, CA, USA), and assembled using SPAdes v.3.10.1. A minimal spanning tree and a neighbour joining tree based on allelic diversity of core-genome multi-locus sequence typing and accessory genes were created using Ridom SeqSphere+ software (Ridom GmbH, Münster, Germany). FINDINGS: Over a 1-year period, 19 VRE carriers were identified; of these, 17 were part of two outbreaks. Before environmental cleaning and disinfection, 55 (14%) environmental samples were VRE-positive. Fifty-one isolates (23 patient samples and 28 environmental samples) were available for WGS analysis. Forty-four isolates were assigned to ST117-vanB, five were assigned to ST17-vanB, and two were assigned to ST80-vanB. Isolates from Outbreak 1 (N=22) and Outbreak 2 (N=22) belonged to ST117-vanB; however, WGS showed a different cluster type with 257 allelic differences. CONCLUSION: WGS of two outbreak strains provided discriminatory information regarding genetic relatedness, and rejected the hypothesis of a common environmental reservoir. A high degree of environmental contamination was associated with higher VRE transmission. Quantification of environmental contamination may reflect the potential for VRE transmission and could therefore support the infection control measures.

The role of insulin resistance in the association between body fat and autonomic function.

BACKGROUND AND AIM: Excess body fat is associated with altered autonomic function. We investigated whether this association is mediated by insulin resistance. METHODS AND RESULTS: Cross-sectional analysis of a subgroup of the Netherlands Epidemiology of Obesity study with measurements of autonomic function (heart rate variability calculated as mean interbeat interval, standard deviation of all normal intervals (SDNN), low frequency (LF) power and high frequency (HF) power). We measured BMI(kg/m²), total body fat(%) and waist circumference(cm), and calculated the HOMA-index of insulin resistance (HOMA-IR). We examined the association between body fat and heart rate variability with multivariate linear regression analysis. To investigate whether the association was mediated by insulin resistance, we additionally adjusted for HOMA-IR. After exclusion of participants with glucose lowering medication (n = 19), 466 participants were included. Per SD of BMI, the difference in SDNN was -2.7% (95%CI: -5.5, 0.1) in the multivariate model. Additional adjustment for HOMA-IR attenuated this association to -1.2% (95%CI: -4.2, 1.7), suggesting that 55% of the association between BMI and SDNN was mediated by HOMA-IR. All measures of body fat were associated with mean interbeat interval, SDNN and LF power. Depending on the parameter of body fat or heart rate variability, 29-81% of the association was mediated by HOMA-IR. CONCLUSION: In this cross-sectional study, body fat was associated with heart rate variability. This association may at least partially be mediated by insulin resistance. Future studies should investigate whether a reduction in obesity and insulin resistance may prevent the adverse cardiovascular consequences of altered autonomic function.

Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement.

BACKGROUND: Adult GH deficiency (GHD) is associated with increased cardiovascular mortality. Recombinant human GH (rhGH) replacement has beneficial short-term metabolic effects. Although these positive effects sustain during longer follow-up, the prevalence of the metabolic syndrome (MS) remains increased in comparison with population data not adjusted for the higher mean BMI in GHD adults. OBJECTIVE: To explore whether middle-aged patients with proposed physiological rhGH replacement have been normalized with respect to MS and its individual components in comparison with the general population, adjusted for age, sex, and BMI. METHODS: One hundred and sixty-one GHD patients (aged 40-70 years) were studied before the start and after 5 years of rhGH replacement, and were compared with 1671 subjects (aged 45-66 years) from the general population (NEO Study). RESULTS: MS PROPORTION IN GHD PATIENTS WAS 41.0% BEFORE THE START OF RHGH SUPPLETION, INCREASING TO 53.4% AFTER 5 YEARS (P=0.007). DESPITE CHRONIC RHGH REPLACEMENT, GHD PATIENTS HAD A 1.3-TIMES HIGHER MS PROPORTION THAN THE GENERAL POPULATION, INDEPENDENTLY OF AGE, SEX, AND BMI (95% CI 1.11.5, P=0.008). THE GHD POPULATION SHOWED A DIFFERENT METABOLIC PROFILE THAN THE GENERAL POPULATION WITH SIMILAR BMI: an increased risk of hypertriglyceridemia (adjusted prevalence ratio (PR) 2.0, 95% CI 1.7-2.3) and low HDL-C (adjusted PR 1.8, 95% CI 1.5-2.2), but less hyperglycemia (adjusted PR 0.5, 95% CI 0.4-0.7). CONCLUSIONS: Despite 5 years of rhGH replacement, GHD patients still have a different metabolic profile and more frequently MS than the general population. These differences were independent of BMI, and resemble the unfavorable metabolic profile of untreated GHD patients, pointing to question the long-term benefits of rhGH replacement.