A novel characterized multi-drug-resistant Pseudocitrobacter sp. isolated from a patient colonized while admitted to a tertiary teaching hospital.

BACKGROUND: Reports of nosocomial infections typically describe recognised microorganisms. Here, a novel bacterial species was isolated, based on rectal swab screening for carbapenemases post-admission, then phenotypically and genetically characterized. METHODS: Sensititre, Vitek and API kits, MALDI and Illumina MiSeq were employed before profiles and phylogeny were compared with other related species. FINDINGS: Determined to be a possible Enterobacterales, the isolate was found to have 99.7% 16s rRNA identity to Pseudocitrobacter corydidari; an Asian cockroach-associated species. Given the highly conserved/low variability of 16S rRNA genes in Enterobacterales, average nucleotide identity (ANI) analysis compared the new isolate's genome with those of 18 Enterobacteriaceae species, including confirmed species of Pseudocitrobacter and unnamed Pseudocitrobacter species in the SILVA database. Of these, Pseudocitrobactercorydidari had the highest ANI at 0.9562. The published genome of the only known isolate of P.corydidari does not include Antimicrobial Resistance Genes (ARGs), with exception of potential drug efflux transporters. In contrast, our clinical isolate bears recognised antimicrobial resistance genes, including Klebsiella pneumoniae carbapenemase. The associated genome suggests resistance to carbapenems, ß-lactams, sulfonamides, fluoroquinolones, macrolides, aminoglycosides and cephalosporins. Phenotypic antimicrobial resistance was confirmed. CONCLUSION: Evident variations in ARG profiles, human colonization and origin in a clinically relevant niche that is geographically, physically and chemically disparate lend credibility for divergent evolution or, less likely, parallel evolution with P. corydidari. Genome data for this new species have been submitted to GENBANK using the proposed nomenclature Pseudocitrobacter limerickensis. The patient was colonized, rather than infected, and did not require antimicrobial treatment.

Large-scale characterization of hospital wastewater system microbiomes and clinical isolates from infected patients: profiling of multi-drug-resistant microbial species.

BACKGROUND: Hospital-acquired infections (HAIs) and infectious agents exhibiting antimicrobial resistance (AMR) are challenges globally. Environmental patient-facing wastewater apparatus including handwashing sinks, showers and toilets are increasingly identified as sources of infectious agents and AMR genes. AIM: To provide large-scale metagenomics analysis of wastewater systems in a large teaching hospital in the Republic of Ireland experiencing multi-drug-resistant HAI outbreaks. METHODS: Wastewater pipe sections (N=20) were removed immediately prior to refurbishment of a medical ward where HAIs had been endemic. These comprised toilet U-bends, and sink and shower drains. Following DNA extraction, each pipe section underwent metagenomic analysis. FINDINGS: Diverse taxonomic and resistome profiles were observed, with members of phyla Proteobacteria and Actinobacteria dominating (38.23 ± 5.68% and 15.78 ± 3.53%, respectively). Genomes of five clinical isolates were analysed. These AMR bacterial isolates were from patients >48 h post-admission to the ward. Genomic analysis determined that the isolates bore a high number of antimicrobial resistance genes (ARGs). CONCLUSION: Comparison of resistome profiles of isolates and wastewater metagenomes revealed high degrees of similarity, with many identical ARGs shared, suggesting probable acquisition post-admission. The highest numbers of ARGs observed were those encoding resistance to clinically significant and commonly used antibiotic classes. Average nucleotide identity analysis confirmed the presence of highly similar or identical genomes in clinical isolates and wastewater pipes. These unique large-scale analyses reinforce the need for regular cleaning and decontamination of patient-facing hospital wastewater pipes and effective infection control policies to prevent transmission of nosocomial infection and emergence of AMR within potential wastewater reservoirs.

Whole-genome sequencing to investigate transmission of SARS-CoV-2 in the acute healthcare setting: a systematic review.

BACKGROUND: Whole-genome sequencing (WGS) has been used widely to elucidate transmission of SARS-CoV-2 in acute healthcare settings, and to guide infection, prevention, and control (IPC) responses. AIM: To systematically appraise available literature, published between January 1st, 2020 and June 30th, 2022, describing the implementation of WGS in acute healthcare settings to characterize nosocomial SARS-CoV-2 transmission. METHODS: Searches of the PubMed, Embase, Ovid MEDLINE, EBSCO MEDLINE, and Cochrane Library databases identified studies in English reporting the use of WGS to investigate SARS-CoV-2 transmission in acute healthcare environments. Publications involved data collected up to December 31st, 2021, and findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. FINDINGS: In all, 3088 non-duplicate records were retrieved; 97 met inclusion criteria, involving 62 outbreak analyses and 35 genomic surveillance studies. No publications from low-income countries were identified. In 87/97 (90%), WGS supported hypotheses for nosocomial transmission, while in 46 out of 97 (47%) suspected transmission events were excluded. An IPC intervention was attributed to the use of WGS in 18 out of 97 (18%); however, only three (3%) studies reported turnaround times ≤7 days facilitating near real-time IPC action, and none reported an impact on the incidence of nosocomial COVID-19 attributable to WGS. CONCLUSION: WGS can elucidate transmission of SARS-CoV-2 in acute healthcare settings to enhance epidemiological investigations. However, evidence was not identified to support sequencing as an intervention to reduce the incidence of SARS-CoV-2 in hospital or to alter the trajectory of active outbreaks.

Hand hygiene practices for prevention of health care-associated infections associated with admitted infectious patients in the emergency department: a systematic review.

BACKGROUND: In most high-income countries, emergency departments (ED) represent the principal point of access forcer by critically ill or injured patients. Unlike inpatient units, ED healthcare workers (ED HCWs) have demonstrated relative lack of adherence to hand hygiene (HH) guidelines, commonly citing frequency of intervention and high rates of admission, which reflect severity of cases encountered. AIM: Assessment of studies on hand hygiene compliance (HHC) by ED HCWs conducted between 2010 and 2020, seeking to estimate HHC rates and intervention strategies utilised to improve HHC in EDs. METHODS: Searches conducted in Web of Science, EBSCO HOST (CINHAL & Medline), PubMed, Embase, and Cochrane for full studies published between 2010 and 2020 on the topic of HHC in the ED. RESULTS: One hundred twenty-nine eligible articles were identified of which 79 were excluded. Fifty-one underwent full-text screening before 20 studies were deemed relevant. Of the eligible studies, fifteen (75%) had, as the primary outcome, HHC according to the WHO-recommended 5-moments. Twelve studies (60%) implemented multimodal or single intervention strategies. Eight studies were ambiguous regarding the nature of the approach adopted. In the nine observational studies where HHC was documented, an overall post-intervention median HHC rate of 45% (range 8-89.7%). CONCLUSION: Multimodal approaches appear to have enhanced HHC moderately among ED HCWs. Elevated complexity associated with critically ill patients, and ED overcrowding, are contributing factors to relatively low compliance rates observed. Strategies to improve HHC rates may need to acknowledge, and cater for, the context of an unpredictable environment.

What is the role of doctors in respect of suspects with mental health and intellectual disabilities in police custody?

People with severe mental illness and intellectual disabilities are overrepresented in the criminal justice system worldwide and this is also the case in Ireland. Following Ireland's ratification of the United Nations' Convention on the Rights of People with Disabilities in 2018, there has been an increasing emphasis on ensuring access to justice for people with disabilities as in Article 13. For people with mental health and intellectual disabilities, this requires a multi-agency approach and a useful point of intervention may be at the police custody stage. Medicine has a key role to play both in advocacy and in practice. We suggest a functional approach to assessment, in practice, and list key considerations for doctors attending police custody suites. Improved training opportunities and greater resources are needed for general practitioners and psychiatrists who attend police custody suites to help fulfill this role.

Advances in e-learning in undergraduate clinical medicine: a systematic review.

BACKGROUND: E-learning is recognised as a useful educational tool and is becoming more common in undergraduate medical education. This review aims to examine the scope and impact of e-learning interventions on medical student learning in clinical medicine, in order to aid medical educators when implementing e-learning strategies in programme curricula. METHODS: A systematic review compliant with PRISMA guidelines that appraises study design, setting and population, context and type of evaluations. Specific search terms were used to locate articles across nine databases: MEDLINE/PubMed, ScienceDirect, EMBASE, Cochrane Library, ERIC, Academic Search Complete, CINAHL, Scopus and Google Scholar. Only studies evaluating e-learning interventions in undergraduate clinical medical education between January 1990 and August 2021 were selected. Of the 4,829 papers identified by the search, 42 studies met the inclusion criteria. RESULTS: The 42 studies included varied in scope, cognitive domain, subject matter, design, quality and evaluation. The most popular approaches involved multimedia platforms (33%) and case-based approaches (26%), were interactive (83%), asynchronous (71%) and accessible from home (83%). Twelve studies (29%) evaluated usability, all of which reported positive feedback. Competence in use of technology, high motivation and an open attitude were key characteristics of successful students and preceptors. CONCLUSIONS: Medical education is evolving consistently to accommodate rapid changes in therapies and procedures. In today's technologically adept world, e-learning is an effective and convenient pedagogical approach for the teaching of undergraduate clinical medicine.

Microbial epidemiology and clinical risk factors of carbapenemase-producing Enterobacterales amongst Irish patients from first detection in 2009 until 2020.

Background: Carbapenemase producing Enterobacterales (CPE) are major public health threats. Aim: To review microbial epidemiology of CPE, as well as clinical risk factors and infections, amongst CPE positive patients over 12 years in an Irish tertiary hospital. Methods: Retrospective observational study of data extracted from a laboratory CPE database, electronic healthcare records and manual review of patient charts. Common risk factors, treatment regimens for all CPE related infections, and clinical outcomes were ascertained. Findings: Among CPE strains isolated from 460 patients, Klebsiella pneumoniae carbapenemase (KPC) was the carbapenemase most frequently detected, accounting for 87.4% (459) of all CPE enzymes. Citrobacter species 177 (33.7%) were the most common species harbouring this enzyme. 428 CPE positive patients (93%) were identified in the acute hospital setting; the most common risk factor for CPE acquisition was history of hospitalisation, observed in 305 (66%) cases. Thirty patients (6.5%) had confirmed infections post-acquisition, of which four were bloodstream infections. There were 19 subsequent episodes of non CPE-related bacteraemia in this cohort. All causal mortality at 30 days was 41 patients (8.9%). However, clinical review determined that CPE was an indirect associative factor in 8 patient deaths. Conclusions: In this tertiary hospital setting, microbial epidemiology is changing; with both OXA-48 enzymes and KPC-producing Citrobacter species becoming more prevalent. Whilst the burden of CPE related infections, especially bacteraemia, was low over the study period, it remains critical that basic infection prevention and control practices are adhered to lest the observed changes in epidemiology result in an increase in clinical manifestations.

Repeated transmission of SARS-CoV-2 in an overcrowded Irish emergency department elucidated by whole-genome sequencing.

AIM: To provide a detailed genomic-epidemiological description of a complex multi-ward SARS-CoV-2 outbreak, which originated in the crowded emergency department (ED) in our hospital during the third wave of the COVID-19 pandemic, and was elucidated promptly by local whole-genome sequencing (WGS). METHODS: SARS-CoV-2 was detected by reverse transcriptase real-time polymerase chain reaction on viral RNA extracted from nasopharyngeal swabs. WGS was performed using an Oxford MinION Mk1C instrument following the ARTIC v3 sequencing protocol. High-quality consensus genomes were assembled with the artic-ncov2019 bioinformatics pipeline and viral phylogenetic trees were built, inferred by maximum-likelihood. Clusters were defined using a threshold of 0-1 single nucleotide polymorphisms (SNPs) between epidemiologically linked sequences. RESULTS: In April 2021, outbreaks of COVID-19 were declared on two wards at University Hospital Limerick after 4 healthcare-associated SARS-CoV-2 infections were detected by post-admission surveillance testing. Contact tracing identified 12 further connected cases; all with direct or indirect links to the ED 'COVID Zone'. All sequences were assigned to the Pangolin B.1.1.7 lineage by WGS, and SNP-level analysis revealed two distinct but simultaneous clusters of infections. Repeated transmission in the ED was demonstrated, involving patients accommodated on trolleys in crowded areas, resulting in multiple generations of infections across three inpatient hospital wards and subsequently to the local community. These findings informed mitigation efforts to prevent cross-transmission in the ED. CONCLUSION: Cross-transmission of SARS-CoV-2 occurred repeatedly in an overcrowded emergency department. Viral WGS elucidated complex viral transmission networks in our hospital and informed infection, prevention and control practice.

Association between tocilizumab treatment of hyperinflammatory patients with COVID-19 in a critical care setting and elevated incidence of hospital-acquired bacterial and invasive fungal infections.

BACKGROUND: Tocilizumab is an interleukin-6 inhibitor that reduces mortality and the need for invasive mechanical ventilation, while increasing the possibility of successful hospital discharge for hyperinflammatory patients with severe coronavirus disease 2019 (COVID-19). No increase in adverse events or serious infections has been reported previously. AIM: To describe the characteristics and outcomes of patients with severe COVID-19 in critical care who received tocilizumab, and to compare mortality and length of hospital stay for patients who received tocilizumab (N=41) with those who did not (N=33). METHODS: Retrospective review of data related to patients with COVID-19 who received tocilizumab in a critical care setting from 1st January to 31st December 2021. FINDINGS: Amongst COVID-19 survivors, those who had received tocilizumab had longer intensive care unit (ICU) stays (median length 21 vs 9 days) and hospital stays (45 vs 34 days) compared with those who had not received tocilizumab. Thirty-day mortality (29% vs 36%; P=0.5196) and 60-day mortality (37% and 42%; P=0.6138) were not significantly lower in patients who received tocilizumab. Serious bacterial and fungal infections occurred at higher frequency amongst patients who received tocilizumab [odds ratio (OR) 2.67, 95% confidence interval (CI) 1.04-6.86; P=0.042], and at significantly higher frequency than in non-COVID-19 ICU admissions (OR 5.26, 95% CI 3.08-9.00; P<0.0001). CONCLUSIONS: In this single-centre study, patients in critical care with severe COVID-19 who received tocilizumab had a greater number of serious bacterial and fungal infections, but this may not have been a direct effect of tocilizumab treatment.

Assessment of the microbial load of airway clearance devices used by a cohort of children with cystic fibrosis.

BACKGROUND: Positive expiratory pressure (PEP) devices are an important element of the management of cystic fibrosis, and of other respiratory diseases. Whereas there have been reports in the literature of contamination of airway clearance devices and their surfaces by microbial pathogens, there is little evidence available regarding such contamination and its contribution to respiratory infection. AIM: To establish whether pathogenic bacteria can contaminate PEP devices in the context of normal cleaning and maintenance practices. METHODS: Patients' home-use clearance devices were brought to a routine clinic appointment and collected for microbiology sampling and analysis. The patients were provided with replacement devices. Nineteen such devices were collected from 17 patients, reflecting use of multiple devices by some patients. Swabs were taken and cultured from each patient's used device, the patient's airway, as well as from new unopened and unused devices that acted as controls. RESULTS: Seven of 19 devices (37%) tested positive for presence of pathogenic bacteria. Device-cleaning methods varied among patients and non-sterilization methods were found to be ineffective at removing pathogens. Microbial species found on the devices did not correlate with those identified from airway swabs. CONCLUSION: This study demonstrates the presence of pathogens on positive expiratory pressure devices. The potential for transmission of these pathogens to the patient's airway and the risk of infection remains unclear and requires further study.

Hand-hygiene-related clinical trials reported between 2014 and 2020: a comprehensive systematic review.

BACKGROUND: There is general consensus that hand hygiene is the most effective way to prevent healthcare-associated infections. However, low rates of compliance amongst healthcare workers have been reported globally. The coronavirus disease 2019 pandemic has further emphasized the need for global improvement in hand hygiene compliance by healthcare workers. AIM: This comprehensive systematic review provides an up-to-date compilation of clinical trials, reported between 2014 and 2020, assessing hand hygiene interventions in order to inform healthcare leaders and practitioners regarding approaches to reduce healthcare-associated infections using hand hygiene. METHODS: CINAHL, Cochrane, EMbase, Medline, PubMed and Web of Science databases were searched for clinical trials published between March 2014 and December 2020 on the topic of hand hygiene compliance among healthcare workers. In total, 332 papers were identified from these searches, of which 57 studies met the inclusion criteria. FINDINGS: Forty-five of the 57 studies (79%) included in this review were conducted in Asia, Europe and the USA. The large majority of these clinical trials were conducted in acute care facilities, including hospital wards and intensive care facilities. Nurses represented the largest group of healthcare workers studied (44 studies, 77%), followed by physicians (41 studies, 72%). Thirty-six studies (63%) adopted the World Health Organization's multi-modal framework or a variation of this framework, and many of them recorded hand hygiene opportunities at each of the 'Five Moments'. However, recording of hand hygiene technique was not common. CONCLUSION: Both single intervention and multi-modal hand hygiene strategies can achieve modest-to-moderate improvements in hand hygiene compliance among healthcare workers.

Outcomes of point-of-care testing for influenza in the emergency department of a tertiary referral hospital in Ireland.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality, and represents a recurring financial burden for community- and hospital-based treatment. Nosocomial outbreaks exacerbate the impact of influenza. Rapid diagnosis of influenza has been shown to reduce transmission. However, point-of-care testing (POCT) in emergency departments and prudent direction of patients with the virus to reduce hospital-acquired infection (HAI) have not been evaluated widely. AIM: To assess performance characteristics of the Abbott ID NOW™ Influenza A & B 2 system, impact on incidence of hospital-acquired influenza, and admission rate ratio for patients who have POCT compared with laboratory testing. POCT was introduced in the 2018-2019 influenza season. Data from then were compared with preceding and subsequent seasons. METHODS: Records of POCT and laboratory testing for the 2017-2018, 2018-2019, and 2019-2020 influenza seasons were analysed. Sensitivity and specificity of POCT were compared pairwise with Xpert Flu A/B/RSV. Patient admission rates and time of waiting for admission were compared. FINDINGS: Compared to laboratory assay, POCT demonstrated sensitivity of 90.6% (95% confidence interval (CI): 78.6-96.5) and specificity of 99.2% (95.2-100) for influenza A, with 51.4% and 41.9% reductions in numbers of HAIs observed in the two seasons when POCT was available, respectively. The admission rate ratio for influenza cases diagnosed by POCT compared with laboratory diagnosis was 0.72 (95% CI: 0.53-0.97; P = 0.031). CONCLUSION: POCT for influenza appears a feasible strategy for testing of patients during peak influenza virus season, with potential to reduce HAI. The relatively rapid turnaround time may also benefit clinical management of patients presenting at emergency departments with suspected influenza.

Role of circulating fibrocytes in the diagnosis of acute appendicitis.

BACKGROUND: Improved diagnostic biomarkers are required for acute appendicitis. The circulating fibrocyte percentage (CFP) is increased in inflammatory states, but has not been studied in acute appendicitis. This study aimed to determine CFP in acute appendicitis and compare diagnostic accuracy with standard serological biomarkers. METHODS: A prospective cohort study was carried out between June 2015 and February 2016 at University Hospital Limerick. The CFP was determined by dual-staining peripheral venous samples for CD45 and collagen I using fluorescence-activated cell sorting, and correlated with histopathological diagnoses. The accuracy of CFP in determining histological acute appendicitis was characterized and compared with the white cell count, C-reactive protein concentration, neutrophil count, lymphocyte count and neutrophil : lymphocyte ratio. RESULTS: Of 95 adults recruited, 15 were healthy individuals and 80 had suspected appendicitis at presentation. Forty-six of these 80 patients had an appendicectomy, of whom 34 had histologically confirmed appendicitis. The CFP was statistically higher in patients with pathologically proven acute appendicitis than in healthy controls (median 6·1 (i.q.r. 1·6-11·6) versus 2·3 (0·9-3·4) per cent respectively; P = 0·008). The diagnostic accuracy of CFP, as determined using the area under the receiver operating characteristic (ROC) curve, was similar to that of standard biomarkers. In multinomial regression analysis, only raised CFP was retained as an independent prognostic determinant of acute appendicitis (odds ratio 1·57, 95 per cent c.i. 1·05 to 2·33; P = 0·027). CONCLUSION: The CFP is increased in histologically confirmed acute appendicitis and is as accurate as standard serological biomarkers in terms of diagnosis.