The BSAC guidelines on treatment of infectious endocarditis (IE) were last published in 2004. The guidelines presented here have been updated and extended to reflect developments in diagnostics, new ...trial data and the availability of new antibiotics. The aim of these guidelines, which cover both native valve and prosthetic valve endocarditis, is to standardize the initial investigation and treatment of IE. An extensive review of the literature using a number of different search criteria has been carried out and cited publications used to support any changes we have made to the existing guidelines. Publications referring to in vitro or animal models have only been cited if appropriate clinical data are not available. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking and therefore a consensus approach has again been adopted for most recommendations; however, we have attempted to grade the evidence, where possible. The guidelines have also been extended by the inclusion of sections on clinical diagnosis, echocardiography and surgery.
The aim of this work was to investigate the microbial causes, incidence, duration, risk factors and clinical implications of bacteraemia occurring during transurethral resection of the prostate ...(TURP) surgery to better inform prophylaxis strategies. An ethically approved, prospective, cohort study of patients undergoing TURP was conducted. Clinical information and follow-up details were collected using standardized data collection sheets. Blood was obtained for culture at 6 different time points peri-procedure. Standard of care antibiotic prophylaxis was given prior to surgery. Bacteriuria was assessed in a pre-procedure urine sample. Histopathology from all prostate chips was assessed for inflammation and malignancy. 73 patients were consented and 276 blood samples obtained. No patients developed symptomatic bacteraemia during the procedure, 17 patients developed asymptomatic bacteraemia (23.2%). Enterococcus faecalis and Pseudomonas aeruginosa were the most common organisms cultured. 10 minutes after the start of the TURP, the odds ratio (OR) of developing bacteraemia was 5.38 (CI 0.97-29.87 p = 0.05), and 20 minutes after the start of the procedure, the OR was 6.46 (CI 1.12-37.24, p = 0.03), compared to before the procedure. We also found an association between the development of intra-operative bacteraemia and recent antibiotic use (OR 4.34, CI 1.14-16.62, p = 0.032), the presence of a urinary catheter (OR 4.92, CI 1.13-21.51, p = 0.034) and a malignant histology (OR 4.90, CI 1.30-18.46, p = 0.019). There was no statistical relationship between pre-operative urine culture results and blood culture results. This study shows that asymptomatic bacteraemia is commonly caused by TURP and occurs in spite of antibiotic prophylaxis. Our findings challenge the commonly held view that urine is the primary source of bacteraemia in TURP-associated sepsis and raise the possibility of occult prostatic infection as a cause of bacteraemia. More work will be needed to determine the significance of transient bacteraemia in relation to more serious complications like infective endocarditis and malignancy.
Infections related to implantable cardiac electronic devices (ICEDs), including pacemakers, implantable cardiac defibrillators and cardiac resynchronization therapy devices, are increasing in ...incidence in the USA and are likely to increase in the UK, because more devices are being implanted. These devices have both intravascular and extravascular components and infection can involve the generator, device leads and native cardiac structures or various combinations. ICED infections can be life-threatening, particularly when associated with endocardial infection, and all-cause mortality of up to 35% has been reported. Like infective endocarditis, ICED infections can be difficult to diagnose and manage. This guideline aims to (i) improve the quality of care provided to patients with ICEDs, (ii) provide an educational resource for all relevant healthcare professionals, (iii) encourage a multidisciplinary approach to ICED infection management, (iv) promote a standardized approach to the diagnosis, management, surveillance and prevention of ICED infection through pragmatic evidence-rated recommendations, and (v) advise on future research projects/audit. The guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies. The questions covered by the guideline are presented at the beginning of each section.
Previous studies of outcomes in people who inject drugs (PWID) with infective endocarditis (IE) have often been retrospective, have had small sample sizes, and the duration of follow-up has been ...short and limited to patients who were operated on.
PWID treated for IE between 1 January 2006 and 31 December 2016 were identified from a prospectively collected database. PWID hospitalized with other infections acted as a novel comparison group. Outcomes were all-cause mortality, cause of death, relapse, recurrence, and reoperation.
There were 105 episodes of IE in 92 PWID and 112 episodes of other infections in 107 PWID in whom IE was suspected but rejected. Survival at 30 days for the IE group was 85%, and 30-day survival following surgery was 96%. The most common pathogens were Staphylococcus species (60%) and Streptococcus species (30%). The surgical intervention rate was 47%. Survival for the IE group at 1, 3, 5, and 10 years was 74%, 63%, 58%, and 44%, respectively. This was significantly lower compared with the comparator group of other infections in PWID (P = .0002). Mortality was higher in patients who required surgery compared with those who did not (hazard ratio, 1.8 95% confidence interval, .95-3.3). The commonest cause of death was infection (66%), usually a further episode of IE (55%).
Although early survival was good, long-term life expectancy was low. This was attributable to ongoing infection risk, rather than other factors known to affect prognosis in PWID. Surgery conferred no long-term survival advantage. More efforts are needed to reduce reinfection risk following an episode of IE in PWID.While early survival for people who inject drugs (PWID) with infective endocarditis is good, long-term survival is poor due to ongoing infection risk. Surgery conferred no long-term survival advantage, so more efforts are needed to reduce reinfection risks for PWID.
The WHO's AWaRe classification categorizes antibiotics into three stewardship groups: Access, Watch and Reserve. The Access group includes antibiotics with lower resistance potential than antibiotics ...in the other two groups. The UK five-year AMR strategy has set targets for reducing non-Access antibiotic use. The majority of penicillins are in the Access group and therefore patients with a penicillin allergy record are likely to receive more non-Access antibiotics. This study aimed to quantify the impact of penicillin allergy records on non-Access antibiotic prescribing and to estimate potential reductions in non-Access antibiotic use through penicillin allergy de-labelling.
Inpatients of a 750-patient-bed UK district general hospital in England prescribed antibiotics between 1st April 2018 and 31st March 2019 were included. Variables included: age, sex, co-morbidity, infection treated, antibiotic usage, hospital length of stay, penicillin allergy status. Multivariable logistic regression was used to explore the association between patient characteristics and their receipt of antibiotics in the Access and non-Access groups.
A total of 67,059 antibiotic prescriptions for 23,356 inpatients were analysed. Penicillin allergy records were present in 14.3% of hospital admissions. Patients with a penicillin allergy record were around four times more likely (odds ratio = 4.7) to receive an antibiotic from the non-Access groups (i.e. Reserve and Watch groups). We estimate de-labelling 50% of hospital inpatients with a penicillin allergy record could reduce non-Access antibiotic use by 5.8% and total antibiotic use by 0.86%.
Penicillin allergy records are associated with non-Access antibiotic prescribing. Penicillin allergy de-labelling has potential to reduce non-Access antibiotic use.
Background: Enterococci frequently cause biofilm infections but susceptibility of clinical isolates growing in biofilms has not been investigated. The minimum biofilm eradicating concentration (MBEC) ...has been suggested as a guide to treatment of biofilm infections. We measured an alternative endpoint, the minimum biofilm inhibitory concentration (MBIC) and compared the results with MIC and MBC. Objectives: To compare the MIC, MBC and MBIC of ampicillin, vancomycin and linezolid against enterococcal biofilms, to assess the impact of additional gentamicin and correlate findings with clinical outcome. Methods: MIC and MBC were measured using standard techniques. MBICs were measured using a modification of the Calgary biofilm device method. Fifty-eight enterococcal isolates from episodes of intravascular catheter-related bloodstream infection were tested. Results: Tolerance to ampicillin, vancomycin and linezolid was seen in 93%, 100% and 93% of isolates, respectively. MIC90s of ampicillin, vancomycin and linezolid were all 4 mg/L for Enterococcus faecalis isolates. MBC90s of ampicillin, vancomycin and linezolid for E. faecalis isolates were 1024, >128 and 2048 mg/L, respectively. MBIC90s of ampicillin, vancomycin and linezolid for E. faecalis isolates were 8192, 4096 and 4096 mg/L, respectively. Results for Enterococcus faecium were similar for vancomycin and linezolid but this species was generally more resistant to ampicillin. Adding 10 mg/L gentamicin had a variable effect on MIC, MBC or MBIC, which was not predictable by gentamicin susceptibility on disc testing. Conclusions: Very high concentrations of ampicillin, vancomycin and linezolid are required to inhibit enterococcal biofilms in vitro. Combining these agents with gentamicin significantly reduced MIC, MBC and MBIC against only a proportion of enterococcal isolates. No correlation between MBIC and outcome was found.
Abstract
Background
Blood biomarkers have the potential to help identify COVID-19 patients with bacterial coinfection in whom antibiotics are indicated. During the COVID-19 pandemic, procalcitonin ...testing was widely introduced at hospitals in the UK to guide antibiotic prescribing. We have determined the impact of this on hospital-level antibiotic consumption.
Methods
We conducted a retrospective, controlled interrupted time series analysis of organization-level data describing antibiotic dispensing, hospital activity and procalcitonin testing for acute hospitals/hospital trusts in England and Wales during the first wave of COVID-19 (24 February to 5 July 2020).
Results
In the main analysis of 105 hospitals in England, introduction of procalcitonin testing in emergency departments/acute medical admission units was associated with a statistically significant decrease in total antibiotic use of −1.08 (95% CI: −1.81 to −0.36) DDDs of antibiotic per admission per week per trust. This effect was then lost at a rate of 0.05 (95% CI: 0.02–0.08) DDDs per admission per week. Similar results were found specifically for first-line antibiotics for community-acquired pneumonia and for COVID-19 admissions rather than all admissions. Introduction of procalcitonin in the ICU setting was not associated with any significant change in antibiotic use.
Conclusions
At hospitals where procalcitonin testing was introduced in emergency departments/acute medical units this was associated with an initial, but unsustained, reduction in antibiotic use. Further research should establish the patient-level impact of procalcitonin testing in this population and understand its potential for clinical effectiveness.
Diagnostic codes from electronic health records are widely used to assess patterns of disease. Infective endocarditis is an uncommon but serious infection, with objective diagnostic criteria. ...Electronic health records have been used to explore the impact of changing guidance on antibiotic prophylaxis for dental procedures on incidence, but limited data on the accuracy of the diagnostic codes exists. Endocarditis was used as a clinically relevant case study to investigate the relationship between clinical cases and diagnostic codes, to understand discrepancies and to improve design of future studies.
Electronic health record data from two UK tertiary care centres were linked with data from a prospectively collected clinical endocarditis service database (Leeds Teaching Hospital) or retrospective clinical audit and microbiology laboratory blood culture results (Oxford University Hospitals Trust). The relationship between diagnostic codes for endocarditis and confirmed clinical cases according to the objective Duke criteria was assessed, and impact on estimations of disease incidence and trends.
In Leeds 2006-2016, 738/1681(44%) admissions containing any endocarditis code represented a definite/possible case, whilst 263/1001(24%) definite/possible endocarditis cases had no endocarditis code assigned. In Oxford 2010-2016, 307/552(56%) reviewed endocarditis-coded admissions represented a clinical case. Diagnostic codes used by most endocarditis studies had good positive predictive value (PPV) but low sensitivity (e.g. I33-primary 82% and 43% respectively); one (I38-secondary) had PPV under 6%. Estimating endocarditis incidence using raw admission data overestimated incidence trends twofold. Removing records with non-specific codes, very short stays and readmissions improved predictive ability. Estimating incidence of streptococcal endocarditis using secondary codes also overestimated increases in incidence over time. Reasons for discrepancies included changes in coding behaviour over time, and coding guidance allowing assignment of a code mentioning 'endocarditis' where endocarditis was never mentioned in the clinical notes.
Commonly used diagnostic codes in studies of endocarditis had good predictive ability. Other apparently plausible codes were poorly predictive. Use of diagnostic codes without examining sensitivity and predictive ability can give inaccurate estimations of incidence and trends. Similar considerations may apply to other diseases. Health record studies require validation of diagnostic codes and careful data curation to minimise risk of serious errors.
In liquid crystal (LC) droplets, small changes in surface anchoring energy can produce large changes in the director field which result in readily detectable optical effects. This makes them ...attractive for use as biosensors. Coating LC droplets with a phospholipid monolayer provides a bridge between the hydrophobic world of LCs and the water-based world of biology and makes it possible to incorporate naturally occurring biosensor systems. However, phos-pholipids promote strong perpendicular (homeotropic) anchoring that can inhibit switching of the director field. We show that the tendency for phospholipid layers to promote perpendicular anchoring can be suppressed by using syn-thetic phospholipids in which the acyl chains are terminated with bulky tert-butyl or ferrocenyl groups; the larger these end-group(s), the less likely the system is to be perpendicular/radial. Additionally, the droplet director field is found to be dependent on the nature of the LC, particularly its intrinsic surface properties; but not (apparently) on the sign of the dielectric anisotropy, the proximity to the melting/isotropic phase transition, the surface tension (in air) or the values of the Frank elastic constants.
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