Comparative genomics and pangenomics of vancomycin-resistant and susceptible Enterococcus faecium from Irish hospitals.

Introduction. Enterococcus faecium has emerged as an important nosocomial pathogen, which is increasingly difficult to treat due to the genetic acquisition of vancomycin resistance. Ireland has a recalcitrant vancomycin-resistant bloodstream infection rate compared to other developed countries.Hypothesis/Gap statement. Vancomycin resistance rates persist amongst E. faecium isolates from Irish hospitals. The evolutionary genomics governing these trends have not been fully elucidated.Methodology. A set of 28 vancomycin-resistant isolates was sequenced to construct a dataset alongside 61 other publicly available Irish genomes. This dataset was extensively analysed using in silico methodologies (comparative genomics, pangenomics, phylogenetics, genotypics and comparative functional analyses) to uncover distinct evolutionary, coevolutionary and clinically relevant population trends.Results. These results suggest that a stable (in terms of genome size, GC% and number of genes), yet genetically diverse population (in terms of gene content) of E. faecium persists in Ireland with acquired resistance arising via plasmid acquisition (vanA) or, to a lesser extent, chromosomal recombination (vanB). Population analysis revealed five clusters with one cluster partitioned into four clades which transcend isolation dates. Pangenomic and recombination analyses revealed an open (whole genome and chromosomal specific) pangenome illustrating a rampant evolutionary pattern. Comparative resistomics and virulomics uncovered distinct chromosomal and mobilomal propensity for multidrug resistance, widespread chromosomal point-mutation-mediated resistance and chromosomally harboured arsenals of virulence factors. Interestingly, a potential difference in biofilm formation strategies was highlighted by coevolutionary analysis, suggesting differential biofilm genotypes between vanA and vanB isolates.Conclusions. These results highlight the evolutionary history of Irish E. faecium isolates and may provide insight into underlying infection dynamics in a clinical setting. Due to the apparent ease of vancomycin resistance acquisition over time, susceptible E. faecium should be concurrently reduced in Irish hospitals to mitigate potential resistant infections.

Humoral response to heterologous prime-booster vaccination in heart transplant recipients aged 18-70 years primed with a viral vector SARS-CoV-2 vaccine.

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2-dose vaccination against SARS-CoV-2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster). Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV-19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS-CoV-2 was the primary outcome measured. This was defined as an anti-spike titre of ≥0.8 U/mL on the Elecsys anti-SARS-CoV-2 S immunoassay. A total of 80 heart transplant patients (mean age 49 ± 13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28-33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p < 0.001). A non-detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p < 0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine basedregimen (p = 0.007). Despite heterologous prime-booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

Humoral response to SARS-CoV-2 adenovirus vector vaccination (ChAdOx1 nCoV-19 [AZD1222]) in heart transplant recipients aged 18 to 70 years of age.

BACKGROUND: Recent studies have suggested a blunted immune response to messenger RNA vaccines in solid organ transplant (SOT) recipients. Given the paucity of data on adenovirus vector vaccines use in immunosuppressed SOT recipients, we sought to describe the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in a heart transplant population. METHODS: Heart transplant recipients aged 18 to 70 years scheduled to receive 2 doses of the ChAdOx1 nCoV-19 vaccine were enrolled into a prospective study involving serum analysis to define their antibody response. An antibody concentration against the spike protein receptor-binding domain of ≥0.8 U/mL was deemed a detectable antibody response. RESULTS: A total of 99 heart transplant recipients (mean age 51 ± 12.5 years, 28% female) were enrolled. No major adverse events were recorded after vaccination; minor symptoms included injection site pain (24%), fatigue (21%) and headache (14%). Of 7 patients with prior SARS-CoV-2 confirmed by PCR testing, all (100%) had detectable antibody responses following first and second vaccine doses. In those with no prior SARS-CoV-2 infection (n = 92), 24% (n = 22) showed an antibody response after dose 1, increasing to 34.8% (n = 32) after dose 2, p < 0.001. Chronic kidney disease (CKD) stage ≥3 (OR 4.7, 95% CI 1.5-15, p = 0.009) and mycophenolate use (OR 4.1, 95% CI 1.2-14, p = 0.02) were independently associated with a nondetectable antibody response. CONCLUSIONS: Almost two-thirds of heart transplant recipients aged 18 to 70 years without a history of prior SARS-CoV-2 infection failed to develop a detectable antibody response following administration of the ChAdOx1 nCoV-19 vaccine. Patient phenotyping may help predict which patients are less likely to develop detectable antibody responses.

Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review.

BACKGROUND: Recent studies have identified the combination of vancomycin with piperacillin-tazobactam (VPT) to be associated with increased nephrotoxicity. Multiple, large cohort studies have found this widely used combination to have a higher risk of nephrotoxicity than other regimens in a variety of populations. SUMMARY: This review summarizes the epidemiology and clinical features of VPT-associated acute kidney injury (AKI). Potential mechanisms involved in the pathogenesis of this phenomenon are also discussed. Key Message: VPT-associated nephrotoxicity is a recently recognized clinical entity. Clinical strategies to minimize the risk of toxicity in this setting include antimicrobial stewardship, monitoring of kidney function, and emerging data supporting the potential role for novel biomarkers in predicting and managing AKI.

Increased Incidence of Central Venous Catheter-Related Infection in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy.

Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) is a complex surgical intervention with associated risks. Central venous catheter (CVC) line sepsis is one of a number of potential morbidities. The aim of this study was to calculate the incidence of catheter-related infection (CRI) in a CRS and HIPEC patient population and to assess its influence on length of hospital stay. Methods: Data were collected on consecutive patients who underwent CRS HIPEC between August 2013 and October 2017. Data included patient demographics, timing of CVC insertion/removal, time spent in critical care, and CVC tip/blood culture results. Charts were reviewed for patients with both positive CVC culture and positive blood cultures to assess for evidence of catheter related infection and systemic inflammatory response syndrome (SIRS). Results: Data on 100 consecutive CRS HIPEC operations performed between August 2013 and October 2017 was analyzed. There were 11 CRIs in 100 CVCs, resulting in a CRI rate of 16.2 per 1,000 CVC days. Patients within the CRI group had a longer high-dependency unit (HDU) stay compared with the non-septic group (6 days vs. 4.07 days, p < 0.05). The CVC duration for the CRI and non-CRI group was 8.4 and 7.6 days, respectively (p = 0.12). The CRI group also had an increased total hospital length of stay (LOS; 20.8 days vs. 15.4 days, p < 0.05). On average, CRIs occurred eight days post-operative and four days post-HDU discharge. There was no association identified with longer CVC duration (p = 0.34). There has been an annual decline in CRI rates in CRS and HIPEC patients over the duration of the study period from 19.1 per 1,000 CVC days in 2016 to 8.2 per 1,000 CVC days in 2017. Conclusion: This is the first study to report on CRI rates in patients undergoing CRS and HIPEC. The CRI rate of 16.2 per 1,000 CVC days is higher than the overall national figure of 5.2 per 1,000 for CVC lines inserted in the operating room. Patients who developed line sepsis had longer HDU and longer overall hospital stay. Catheter-related infection was noted post-HDU discharge in all cases. Implementation of a CVC care bundle in the later years of the study period coincided with a reduction in CRI rates.

Wearable monitors for patients following discharge from an intensive care unit: practical lessons learnt from an observational study.

AIMS: To identify the practical challenges encountered when using wearable monitors for patients discharged from the intensive care unit. BACKGROUND: Patients discharged from intensive care units are a high-risk group that might benefit from continuing observation using 'wearable' monitors to enable faster identification of physiological deterioration and facilitate timely clinical action. This area of technological innovation is of key interest to nurses who manage this group of patients. DESIGN: A prospective observational study. METHODS: An observational study conducted in 2013-2014 used wearable monitors to record continuous observations for patients discharged from an intensive care unit to develop a predictive model of patients likely to deteriorate. Screening data for study eligibility and case report form data to assess monitor tolerance and comfort were collected daily and analysed using Microsoft Access. RESULTS/FINDINGS: Patients (n = 2704) were discharged from an intensive care unit during the study, 208 consented to wearing the monitor. Of the 192 included in analysis, 130 (67·7%) removed the monitor before the trial finished. Reasons cited for removal included 'discomfort and irritation' 61 (31·8%) and 'feeling too unwell' 8 (4·2%). Five hundred seventeen patients were screened following adaption of the wearable monitor. Despite design changes, 56 (10·8%) patients were unable to wear monitors for reasons related to their anatomy or condition. Of 124 patients, 65 patients (52·4%) who were approached refused participation. CONCLUSION: Work is needed to understand wireless monitor comfort and design for acutely unwell patients. Product design needs to develop further, so patients are catered for in flexibility of monitor placement and improved comfort for long-term wear.