Project description:Staphylococcus aureus is a common cause of bacterial infections worldwide. It is most commonly carried in and transmitted from the anterior nares. Hosts are known to vary in their proclivity for S. aureus nasal carriage and may be divided into persistent carriers, intermittent carriers, and noncarriers, depending on duration of carriage. Mathematical models of S. aureus to predict outcomes of interventions have, however, typically assumed that all individuals are equally susceptible to colonization.To characterize biases created by assuming a homogeneous host population in estimating efficacy of control interventions.Mathematical model.We developed a model of S. aureus carriage in the healthcare setting under the homogeneous assumption as well as a heterogeneous model to account for the 3 types of S. aureus carriers. In both models, we calculated the equilibrium carriage prevalence to predict the impact of control measures (reducing contact and decolonization).The homogeneous model almost always underestimates S. aureus transmissibility and overestimates the impact of intervention strategies in lowering carriage prevalence compared to the heterogeneous model. This finding is generally consistent regardless of changes in model setting that vary the proportions of various carriers in the population and the duration of carriage for these carrier types.Not accounting for host heterogeneity leads to systematic and substantial biases in predictions of the effects of intervention strategies. Further understanding of the clinical impacts of heterogeneity through modeling can help to target control measures and allocate resources more efficiently.
Project description:Eczema is a common long-term condition, but inadequate support and information can lead to poor adherence and treatment failure. We have reviewed the international literature of interventions designed to promote self-management in adults and children with eczema. MEDLINE, MEDLINE in process, Embase, CINAHL and the Global Resource for EczemA Trials database were searched from their inception to August 2016, for randomized controlled trials. Two authors independently applied eligibility criteria, assessed risk of bias for all included studies and extracted data. Twenty studies (3028 participants) conducted in 11 different countries were included. The majority (n = 18) were based in secondary care and most (n = 16) targeted children with eczema. Reporting of studies, including descriptions of the interventions and the outcomes themselves, was generally poor. Thirteen studies were face-to-face educational interventions, five were delivered online and two were studies of written action plans. Follow-up in most studies (n = 12) was short term (up to 12 weeks). Only six trials specified a single primary outcome. There was limited evidence of effectiveness. Only three studies collected and reported outcomes related to cost and just one study undertook any formal cost-effectiveness analysis. In summary, we have identified a general absence of well-conducted and well-reported randomized controlled trials with a strong theoretical basis. Therefore, there is still uncertainty about how best to support self-management of eczema in a clinically effective and cost-effective way. Recommendations on design and conduct of future trials are presented.
Project description:Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. A characteristic of atopic eczema (AE) is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism. Despite this, the origins and genetic diversity of S. aureus colonizing individual patients during AE disease flares is poorly understood. To examine the microevolution of S. aureus colonization, we deep sequenced S. aureus populations from nine children with moderate to severe AE and 18 non-atopic children asymptomatically carrying S. aureus nasally. Colonization by clonal S. aureus populations was observed in both AE patients and control participants, with all but one of the individuals carrying colonies belonging to a single sequence type. Phylogenetic analysis showed that disease flares were associated with the clonal expansion of the S. aureus population, occurring over a period of weeks to months. There was a significant difference in the genetic backgrounds of S. aureus colonizing AE cases versus controls (Fisher exact test, P = 0.03). Examination of intra-host genetic heterogeneity of the colonizing S. aureus populations identified evidence of within-host selection in the AE patients, with AE variants being potentially selectively advantageous for intracellular persistence and treatment resistance.
Project description:PurposeStaphylococcus aureus is the critical pathogenic bacterium of eczema. The relationship between nasal colonization by S. aureus and eczema has not been well studied. We aimed to evaluate the associations between nasal colonization by S. aureus and eczema of multiple body sites, including persistent and ever-reported eczema. We further examined the associations between eczema and different subtypes of S. aureus, that is, methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA).MethodsThe real-world data from the US National Health and Nutrition Examination Survey were used. The associations were calculated using survey-weighted multinomial logistic regression models and further calculated in subgroups stratified by demographic factors.ResultsIn total, 2,941 adults were included. The prevalence rate of S. aureus nasal carriage was significantly higher in adults with persistent hand eczema (51.0%) than in those with ever-reported hand eczema (23.3%) and never eczema (26.9%). S. aureus nasal colonization was associated with an approximately two-fold increased risk of persistent hand eczema (odds ratios ranges in different models: 2.86-3.06) without significant heterogeneity in the association by demographic factors. No significant associations between S. aureus nasal colonization and persistent eczema of other body sites or ever-reported eczema of multiple body sites (including hands) were observed. Furthermore, similar significant association between nasal colonization of MSSA and persistent hand eczema was seen; the association was much stronger (odds ratios ranges in different models: 4.64-6.54) for MRSA, although with borderline significant.ConclusionsNasal colonization of S. aureus was associated with increased risk of persistent hand eczema. Our findings imply that preventive measures targeting S. aureus for the anterior nares should be considered in preventing and treating eczema.
Project description:The human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens such as methicillin-resistant Staphylococcus aureus can reside within the nasal microbiota which increases the risk of infections. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species and S. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration but their role in the nasal microbiome is unknown. Here we show that siderophore acquisition is crucial for S. aureus nasal colonization in vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced by S. aureus. We found that 80% of the strains engaged in siderophore mediated interactions with S. aureus. Non-pathogenic corynebacterial species were found to be prominent consumers of S. aureus siderophores. In co-culture experiments, consumption of siderophores by competitors reduced S. aureus growth in an iron dependent fashion. Our data show a wide network of siderophore mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displace S. aureus from the nasal cavity of humans.
Project description:Several management strategies may improve outcomes in patients with Staphylococcus aureus bacteremia.To review evidence of management strategies for S. aureus bacteremia to determine whether transesophageal echocardiography is necessary in all adult cases and what is the optimal antibiotic therapy for methicillin-resistant S. aureus (MRSA) bacteremia.A PubMed search from inception through May 2014 was performed to identify studies addressing the role of transesophageal echocardiography in S. aureus bacteremia. A second search of PubMed, EMBASE, and the Cochrane Library from January 1990 through May 2014 was performed to find studies addressing antibiotic treatment for MRSA bacteremia. Studies reporting outcomes from antibiotic therapy for MRSA bacteremia were included. All searches, which were limited to English and focused on adults, were augmented by review of bibliographic references from included studies. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation system with consensus of independent evaluations by at least 2 of the authors.In 9 studies with a total of 4050 patients, use of transesophageal echocardiography was associated with higher rates of a diagnosis of endocarditis (14%-28%) compared with transthoracic echocardiography (2%-15%). In 4 studies, clinical or transthoracic echocardiography findings did not predict subsequent transesophageal echocardiography findings of endocarditis. Five studies identified clinical or transthoracic echocardiography characteristics associated with low risk of endocarditis (negative predictive values from 93% to 100%). Characteristics associated with a low risk of endocarditis include absence of a permanent intracardiac device, sterile follow-up blood cultures within 4 days after the initial set, no hemodialysis dependence, nosocomial acquisition of S. aureus bacteremia, absence of secondary foci of infection, and no clinical signs of infective endocarditis. Of 81 studies of antibiotic therapy for MRSA bacteremia, only 1 high-quality trial was identified. In that study of 246 patients with S. aureus bacteremia, daptomycin was not inferior to vancomycin or an antistaphylococcal penicillin, each in combination with low-dose, short-course gentamicin (clinical success rate, 44.2% [53/120] vs 41.7% [48/115]; absolute difference, 2.4% [95% CI, -10.2% to 15.1%]).All adult patients with S. aureus bacteremia should undergo echocardiography. Characteristics of low-risk patients with S. aureus bacteremia for whom transesophageal echocardiography can be safely avoided have been identified. Vancomycin and daptomycin are the first-line antibiotic choices for MRSA bacteremia. Well-designed studies to address the management of S. aureus bacteremia are needed.
Project description:Staphylococcus aureus bacteraemia is a serious infection associated with significant complications, including recurrence of bacteraemia, endocarditis and metastatic foci of infection. The management of these patients is often complex, involving appropriate source control, a thorough review and investigations to exclude metastatic foci and infective endocarditis. Additionally, a prolonged course of intravenous antibiotics is often required. As part of our quality improvement project, the following five aspects were evaluated in 56 patients with S. aureus bacteraemia at two District General Hospitals: 1) adequate and timely removal of the source of bacteraemia, 2) echocardiography to exclude endocarditis, 3) repeat blood culture to prove clearance of bacteraemia, 4) adequate duration and choice of antibiotics and 5) documentation of bacteraemia in the discharge summary. After an initial review revealed several areas for improvement, we instituted five Plan-Do-Study-Act learning cycles which involved: teaching microbiology trainees and junior doctors, improving clinical liaison and communication between the microbiology team and clinicians, as well as a clinical review of patients by the microbiology team where appropriate. The post-intervention review evaluated 24 patients with S. aureus bacteraemia between November 2012 and May 2013. The proportion of patients undergoing an echocardiogram improved from 49% to 88%. Another marked improvement was seen in the timely obtaining of clearance blood cultures, with 88% of patients having clearance blood cultures within the 2-4 day window, compared to 56% pre-intervention. 70% of patients with uncomplicated S. aureus bacteraemia received an appropriate antibiotic course post-intervention, compared with 59% pre-intervention. Documentation of the S. aureus bacteraemia in the discharge summary improved from 65% to 75%. The support of the entire microbiology team was pivotal in the successful outcome of the quality improvement project.
Project description:Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.
Project description:Staphylococcus aureus is a common skin commensal with the potential to cause severe infections resulting in significant morbidity and mortality. Up to 30% of individuals are colonized with S aureus, though infection typically does not occur without skin barrier disruption. Infection management includes promptly addressing the source of infection, including sites of metastatic infection, and initiation of effective antibiotics, which should be selected based on local antibiotic susceptibility patterns. Given that S aureus colonization is a risk factor for infection, preventive strategies are aimed at optimizing hygiene measures and decolonization regimens for outpatients and critically ill children with prolonged hospitalizations.