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Antibiotic prophylaxis given before invasive dental procedures in patients at risk of developing infective endocarditis has historically been the focus of infective endocarditis prevention. Recent changes in antibiotic prophylaxis guidelines in the USA and Europe have substantially reduced the number of patients for whom antibiotic prophylaxis is recommended. In the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) recommended complete cessation of antibiotic prophylaxis for prevention of infective endocarditis in March, 2008. We aimed to investigate changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis since the introduction of these guidelines. We did a retrospective secular trend study, analysed as an interrupted time series, to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England. We analysed data for the prescription of antibiotic prophylaxis from Jan 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of infective endocarditis from Jan 1, 2000, to March 31, 2013. We compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series. Prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis fell substantially after introduction of the NICE guidance (mean 10 900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], p<0·0001). Starting in March, 2008, the number of cases of infective endocarditis increased significantly above the projected historical trend, by 0·11 cases per 10 million people per month (95% CI 0·05–0·16, p<0·0001). By March, 2013, 35 more cases per month were reported than would have been expected had the previous trend continued. This increase in the incidence of infective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk. Although our data do not establish a causal association, prescriptions of antibiotic prophylaxis have fallen substantially and the incidence of infective endocarditis has increased significantly in England since introduction of the 2008 NICE guidelines. Heart Research UK, Simplyhealth, and US National Institutes of Health.

BackgroundThe current diagnosis of infective endocarditis (IE) is based on the modified Duke criteria, which has approximately 80% sensitivity for the diagnosis of native valve endocarditis (NVE), with lower sensitivity for the diagnosis of prosthetic valve endocarditis (PVE) and culture-negative endocarditis. There is preliminary evidence that 18F-FDG PET/CT is an adjunctive diagnostic test with high accuracy reported in small studies to date. We therefore performed a meta-analysis of studies evaluating the use of PET/CT in the diagnosis of IE to establish a more precise estimate of accuracy.MethodsPubMed, Embase, Cochrane library, CINAHL, Web of Knowledge, and www.clinicaltrials.gov were searched from January 1990 to April 2017 for studies evaluating the accuracy of PET/CT for the evaluation of possible IE.ResultsWe identified 13 studies involving 537 patients that were included in the meta-analysis. The pooled sensitivity of PET/CT for diagnosis of IE was 76.8% (95% CI 71.8–81.4%; Q = 39.9, P < 0.01; I2 = 69.9%) and the pooled specificity was 77.9% (95% CI 71.9–83.2%; Q = 44.42, P < 0.01; I2 = 73.0%). Diagnostic accuracy was improved for PVE with sensitivity of 80.5% (95% CI 74.1–86.0%; Q = 25.5, P < 0.01; I2 = 72.5%) and specificity of 73.1% (95% CI 63.8–81.2%; Q = 32.1, P < 0.01; I2 = 78.2%). Additional extracardiac foci of infection were found on 17% of patients on whole body PET/CT.ConclusionPET/CT is a useful adjunctive diagnostic tool in the evaluation of diagnostically challenging cases of IE, particularly in prosthetic valve endocarditis. It also has the potential to detect clinically relevant extracardiac foci of infection, malignancy, and other sources of inflammation leading to more appropriate treatment regimens and surgical intervention.

Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus . This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention.

[...]use of antibiotics before invasive dental procedures in patients who are at risk is a long-held preventive measure; however, antibiotic prophylaxis remains controversial. Since 2007, international guidelines have recommended that antibiotic prophylaxis should be restricted to patients at the highest risk of adverse outcomes—ie, those with a history of infective endocarditis, prosthetic or repaired heart valves, or complex congenital heart disease. Multiple contributory factors are probable, including an ageing population, increased use of both intracardiac (eg, permanent pacemakers, implantable cardioverter defibrillators, or surgical and transcatheter heart valves) and vascular devices (eg, those used for chronic haemodialysis), epidemic levels of opioid addiction and associated injection drug use, emergence of staphylococci and enterococci (neither of which are targeted by antibiotic prophylaxis strategies) as more common causative organisms, and improved clinical awareness of infective endocarditis. Greater public health awareness and further investigation are warranted of the causes responsible for this alarming increase in the incidence of infective endocarditis in England, alongside renewed emphasis on education of patients at risk, maintenance of good oral hygiene, early disease diagnosis, timely referral, and specialist care.

ObjectiveNon-bacterial thrombotic endocarditis (NBTE) is a syndrome characterised by cardiac valve vegetations and/or thickening due to non-infective mechanisms. Nowadays, a premortem diagnosis of NBTE is possible based on echocardiographic findings. Therefore, to better characterise this disease, we performed a contemporary review of the epidemiology, demographics, diagnosis and clinical outcomes of these patients.MethodsAdults with a diagnosis of NBTE seen within the Mayo Clinic Enterprise from December 2014 to December 2021 were included. NBTE diagnosis was identified by clinicians representing at least two specialties including cardiology, infectious diseases, rheumatology and oncology. Patients with positive blood cultures, infective endocarditis, culture-negative endocarditis and denial of research authorisation were excluded. All patients had a 1-year follow-up.ResultsForty-eight cases were identified; mean age was 60.0±13.8 years, 75% were female. The most prevalent comorbidities were malignancy (52.1%) and connective tissue disease (37.5%). Valvular abnormalities included 41 (85.4%) patients with vegetations, 43 (89.6%) patients with thickening and 26 (54.2%) with moderate to severe regurgitation. Thirty-eight (79.2%) patients had an embolic event (stroke in 26 (54.2%) patients) within 1 month of NBTE diagnosis and 16 (33.3%) patients died within 1 year of NBTE diagnosis. Metastatic tumours and lung cancer were associated with 1-year all-cause mortality (p=0.0017 and p=0.0004, respectively).ConclusionsNBTE was more prevalent in females and embolic complications were the most frequent clinical finding. Overall, patients with NBTE had a poor prognosis, particularly in those with lung cancer or metastatic tumours. Further studies in patients with NBTE are needed given its morbidity and mortality.

Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I(2) = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26-1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship.

The aim of this study is to determine if there have been contemporary shifts in infective endocarditis (IE) epidemiology in our local population; an analysis of cases from 2007 to 2013 was conducted. This is a population-based review of all adults (≥18 years) residing in Olmsted County, MN, with definite or possible IE using the Rochester Epidemiology Project from January 1, 2007, to December 31, 2013. We identified 51 cases of IE in Olmsted County, MN, between 2007 and 2013. Median age of IE cases was 68.8 years (interquartile range 55.6-76.5), and 41% were females. Age- and sex-adjusted incidence of IE was 7.4 (95% CI 5.3-9.4) cases per 100,000 person-years. From a multivariable Poisson regression model, incidence of IE did not change significantly during the study period (P = .222) but was significantly higher in males and those of older age (P < .001). The annual incidences (per 100,000 person-years) were 2.5 for Staphylococcus aureus, 1.1 for viridans group streptococci, 1.6 for Enterococcus species, and 0.8 for coagulase-negative staphylococci. Only 19.6% (10/51) of Olmsted County patients underwent valve surgery between 2007 and 2013 as compared with 44.4% (197/444) of non–Olmsted County patients treated at Mayo Clinic Rochester. In this population-based study, no significant change in the overall incidence of IE in Olmsted County, MN, between 2007 and 2013 was seen, and it was similar to that seen between 1970 and 2006. Male gender and older age were associated with increased IE risk. With a lesser extent of cases attributable to viridans group streptococcal IE compared with previous years, S aureus was the predominant pathogen in IE cases during 2007 to 2013. The relatively low valve surgery rate was disparate from that reported from large, tertiary care centers (including our own) with non–population-based cohorts, which are subject to referral bias and can influence the expected characterization of IE.

As cardiac implantable electronic devices become increasingly common, infections (generally caused by staphylococci) are also more frequent. In addition to antibiotic therapy, complete removal of the device is required for cure. Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage A 75-year-old man presents with localized pain, redness, and swelling of 3 weeks' duration at the pocket site in the left upper shoulder, where an implantable cardioverter–defibrillator was placed 6 months earlier. He has no fever or other systemic symptoms. Physical examination reveals redness and induration at the site of the generator pocket on the left shoulder, with no stigmata of infective endocarditis. Results of blood cultures are negative. How should this case be managed? The Clinical Problem The use of cardiovascular implantable electronic devices (CIEDs) has increased in recent years, owing largely to the expansion of their functions . . .

AimTo provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe.MethodsA systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence.ResultsOf 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%.ConclusionBased on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase.Trial registeration numberCRD42020191196.

Introduction Dentists prescribe a significant proportion of all antibiotics, while antimicrobial stewardship aims to minimise antibiotic-prescribing to reduce the risk of developing antibiotic-resistance and adverse drug reactions.Aims To evaluate NHS antibiotic-prescribing practices of dentists in England between 2010-2017.Methods NHS Digital 2010-2017 data for England were analysed to quantify dental and general primary-care oral antibiotic prescribing.Results Dental prescribing accounted for 10.8% of all oral antibiotic prescribing, 18.4% of amoxicillin and 57.0% of metronidazole prescribing in primary care. Amoxicillin accounted for 64.8% of all oral antibiotic prescribing by dentists, followed by metronidazole (28.0%), erythromycin (4.4%), phenoxymethylpenicillin (0.9%), clindamycin (0.6%), co-amoxiclav (0.5%), cephalosporins (0.4%) and tetracyclines (0.3%). Prescriptions by dentists declined during the study period for all antibiotics except for co-amoxiclav. This increase is of concern given the need to restrict co-amoxiclav use to infections where there is no alternative. Dental prescribing of clindamycin, which accounted for 43.9% of primary care prescribing in 2010, accounted for only 14.6% in 2017. Overall oral antibiotic prescribing by dentists fell 24.4% as compared to 14.8% in all of primary care.Conclusions These data suggest dentists have reduced antibiotic prescribing, possibly more than in other areas of primary-care. Nonetheless, opportunities remain for further reduction.