Explore the vast range of titles available.

Invasive fungal diseases are an important cause of morbidity and mortality in a wide range of patients, and early diagnosis and management are a challenge. We therefore did a review of the scientific literature to generate a series of key recommendations for the appropriate use of microbiological, histological, and radiological diagnostic methods for diagnosis of invasive fungal diseases. The recommendations emphasise the role of microscopy in rapid diagnosis and identification of clinically significant isolates to species level, and the need for susceptibility testing of all Aspergillus spp, if treatment is to be given. In this Review, we provide information to improve understanding of the importance of antigen detection for cryptococcal disease and invasive aspergillosis, the use of molecular (PCR) diagnostics for aspergillosis, and the crucial role of antibody detection for chronic and allergic aspergillosis. Furthermore, we consider the importance of histopathology reporting with a panel of special stains, and emphasise the need for urgent (<48 hours) and optimised imaging for patients with suspected invasive fungal infection. All 43 recommendations are auditable and should be used to ensure best diagnostic practice and improved outcomes for patients.

Background Candida auris is a globally emerging multidrug resistant fungal pathogen causing nosocomial transmission. We report an ongoing outbreak of C. auris in a London cardio-thoracic center between April 2015 and July 2016. This is the first report of C. auris in Europe and the largest outbreak so far. We describe the identification, investigation and implementation of control measures. Methods Data on C. auris case demographics, environmental screening, implementation of infection prevention/control measures, and antifungal susceptibility of patient isolates were prospectively recorded then analysed retrospectively. Speciation of C. aur is was performed by MALDI-TOF and typing of outbreak isolates performed by amplified fragment length polymorphism (AFLP). Results This report describes an ongoing outbreak of 50 C. auris cases over the first 16 month (April 2015 to July 2016) within a single Hospital Trust in London. A total of 44 % ( n  = 22/50) patients developed possible or proven C. auris infection with a candidaemia rate of 18 % ( n  = 9/50). Environmental sampling showed persistent presence of the yeast around bed space areas. Implementation of strict infection and prevention control measures included: isolation of cases and their contacts, wearing of personal protective clothing by health care workers, screening of patients on affected wards, skin decontamination with chlorhexidine, environmental cleaning with chorine based reagents and hydrogen peroxide vapour. Genotyping with AFLP demonstrated that C. auris isolates from the same geographic region clustered. Conclusion This ongoing outbreak with genotypically closely related C. auris highlights the importance of appropriate species identification and rapid detection of cases in order to contain hospital acquired transmission.

Candida auris was first described in 2009, and it has since caused nosocomial outbreaks, invasive infections, and fungaemia across at least 19 countries on five continents. An outbreak of C. auris occurred in a specialized cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak in the UK, involving a total of 72 patients. To understand the genetic epidemiology of C. auris infection both within this hospital and within a global context, we sequenced the outbreak isolate genomes using Oxford Nanopore Technologies and Illumina platforms to detect antifungal resistance alleles and reannotate the C. auris genome. Phylogenomic analysis placed the UK outbreak in the India/Pakistan clade, demonstrating an Asian origin; the outbreak showed similar genetic diversity to that of the entire clade, and limited local spatiotemporal clustering was observed. One isolate displayed resistance to both echinocandins and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FKS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1. These mutations add to a growing body of research on multiple antifungal drug targets in this organism. Multiple differential episodic selection of antifungal resistant genotypes has occurred within a genetically heterogenous population across this outbreak, creating a resilient pathogen and making it difficult to define local-scale patterns of transmission and implement outbreak control measures.

Ficolins are innate pattern recognition receptors (PRR) and play integral roles within the innate immune response to numerous pathogens throughout the circulation, as well as within organs. Pathogens are primarily removed by direct opsonisation following the recognition of cell surface carbohydrates and other immunostimulatory molecules or via the activation of the lectin complement pathway, which results in the deposition of C3b and the recruitment of phagocytes. In recent years, there have been a number of studies implicating ficolins in the recognition and removal of numerous bacterial, viral, fungal, and parasitic pathogens. Moreover, there has been expanding evidence highlighting that mutations within these key immune proteins, or the possession of particular haplotypes, enhance susceptibility to colonization by pathogens and dysfunctional immune responses. This review will therefore encompass previous knowledge on the role of ficolins in the recognition of bacterial and viral pathogens, while acknowledging the recent advances in the immune response to fungal and parasitic infections. Additionally, we will explore the various genetic susceptibility factors that predispose individuals to infection.

[...]studies have highlighted that they may be used as a possible alternative to current antifungal drugs or used in combination to increase efficacy [3]. To date, there has been no indication that soluble PRRs can be exploited for their diagnostic potential, albeit the presence of PRRs such as L-ficolin and MBL in the lung during inflammation and infection highlights the necessity to investigate soluble PRRs as potential diagnostic tools. [...]larger-scale clinical trials are needed to assess the full diagnostic potential of ficolins and other PRRs in combination with current fungal and host biomarkers in order to evaluate their role in diagnostics and possible impact on patient outcomes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fungal infections are increasingly prevalent; however, antifungal stewardship attracts little funding or attention. Previous studies have shown that knowledge of guidelines and scientific evidence regarding antifungals is poor, leading to prescribing based on personal experiences and the inherent biases this entails. We carried out a retrospective study of inpatient antifungal usage at two major hospitals. We assessed the longitudinal trends in antifungal usage and the effect of COVID-19 on antifungal prescription, alongside levels of empirical and diagnostically targeted antifungal usage. Our results showed that the longitudinal patterns of total systemic antifungal usage within the trusts were similar to national prescribing trends; however, the composition of antifungals varied considerably, even when looking exclusively at the more homogenous group of COVID-19 patients. We showed a high level of empirical antifungal use in COVID-19 patients, with neither trust adhering to international recommendations and instead appearing to follow prior prescribing habits. This study highlights the significant challenges to optimise antifungal use with prescribing behaviour largely dictated by habit, a lack of adherence to guidelines, and high rates of empirical non-diagnostic-based prescribing. Further research and resources are required to understand the impact of antifungal stewardship on improving antifungal prescribing behaviours in this setting and the effects on outcome.

Aspergillus fumigatus has been found to coinfect patients with severe SARS-CoV-2 virus infection, leading to COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole resistance. Genomic epidemiology can help shed light on the genetics of A. fumigatus causing CAPA, including the prevalence of resistance-associated alleles. We present a population genomic analysis of 21 CAPA isolates from four European countries with these isolates compared against 240 non-CAPA A. fumigatus isolates from a wider population. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically encoded azole-resistant mechanisms. The phylogenetic analysis of the 21 CAPA isolates showed that they were representative of the wider A. fumigatus population with no obvious clustering. The prevalence of phenotypic azole resistance in CAPA was 14.3% (n = 3/21); all three CAPA isolates contained a known resistance-associated cyp51A polymorphism. The relatively high prevalence of azole resistance alleles that we document poses a probable threat to treatment success rates, warranting the enhanced surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes when CAPA is suspected.

Infective endocarditis in dialysis patients: New challenges and old. Since the 1960s chronic hemodialysis (HD) has been recognized as a risk factor for the development of infective endocarditis (IE). Historically, it has been particularly associated with vascular access via dual lumen catheters. We wished to examine the risk factors for, and consequences of, IE in the modern dialysis era. Cases of IE (using the Duke criteria) at St. Thomas' Hospital (1980 to 1995), Guy's (1995 to 2002), and King's College Hospitals (1996 to 2002) were reviewed. Twenty-eight patients were identified as having developed IE (30 episodes of IE). Twenty-seven patients were on long-term HD and one patient was on peritoneal dialysis (PD). Mean age was 54.1years, and mean duration of HD prior to IE was 46.3months. Eight patients were diabetic. Primary HD hemoaccess was an arteriovenous fistula (AVF) in 41.3%, a dual-lumen tunneled catheter (DLTC) in 37.9%, a polytetrafluoroethylene (PTFE) graft in 10.3%, and a dual-lumen non-tunneled catheter (DLNTC) in 4%. The presumed source of sepsis was directly related to hemoaccess in 25 HD patients: DLTC in 48%; AVF in 32%; PTFE in 12%; and DLNTC in 4%. Staphylococcus aureus[including methicillin resistant Staphylococcus aureus (MRSA)] was present in 63.3%. The mitral valve was affected in 41.4% of patients, aortic valve in 37.9% of patients, and both valves were affected in 17.2% of patients. Of note, 51.7% of patients had an abnormal valve before the episode of IE. In 15 cases surgery was undertaken. Fourteen patients survived to discharge, and 12 survived for 30days. In 15 cases antibiotic treatment alone was employed; in this case, eight patients died and seven survived to discharge. This is the largest reported confirmed IE series in dialysis patients. Infective endocarditis in HD patients remains a challenging problem—although hemoaccess via dual-lumen catheters remains a significant risk, many cases developed in patients with AVFs and this group suffered the greatest mortality. An abnormal valve (frequently calcified) was another risk factor; because valve calcification is now common after 5years on dialysis, more effort in preventing this avoidable form of ectopic calcification may reduce the risk of developing IE.