A multicentre observational study to investigate feasibility of a direct oral penicillin challenge in de-labelling 'low risk' patients with penicillin allergy by non-allergy healthcare professionals (SPACE study): Implications for healthcare systems.

OBJECTIVE: The huge burden of inaccurate penicillin allergy labels (PALs) is an important driver of antimicrobial resistance. This is magnified by insufficient allergy specialists and lack of 'point-of-care' tests. We investigated the feasibility of non-allergy healthcare professionals (HCPs) delivering direct oral penicillin challenges (DPCs) for penicillin allergy de-labelling. METHODS: This prospective observational study was conducted in three hospitals in England across three settings (acute medical, pre-surgical and haematology-oncology). Patients with a PAL were screened and stratified as low risk/high risk. Low risk patients (non-immune mediated symptoms, benign rash, tolerated amoxicillin since and family history) underwent a DPC. RESULTS: N = 2257 PALs were screened, 1054 were eligible; 643 were approached, 373 declined, 270 consented and 259 risk stratified (low risk = 155; high risk = 104). One hundred and twenty-six low risk patients underwent DPC, 122 (96.8%) were de-labelled with no serious allergic reactions. Conversion rate from screening-to-consent was 12% [3.3% and 17.9% in acute and elective settings respectively; odds ratios for consent were 3.42 (p < 0.001) and 5.53 (p < 0.001) in haematology-oncology and pre-surgical setting respectively. Common reasons for failure to progress in the study included difficulty in reaching patients, clinical instability/medical reasons, lacking capacity to consent and psychological factors. INTERPRETATION: DPCs can be delivered by non-allergy HCPs. A high proportion of patients with PALs did not progress in the study pathway. Strategies to deliver DPC at optimal points of the care pathway are needed to enhance uptake. Elective settings offer greater opportunities than acute settings for DPC. The safety and simplicity of DPCs lends itself to adoption by healthcare systems beyond the UK, including in resource-limited settings.

Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial.

INTRODUCTION: Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England. Penicillin allergy records are associated with worse health outcome and antimicrobial resistance. The ALlergy AntiBiotics And Microbial resistAnce (ALABAMA) trial aims to determine if an intervention package, centred around a penicillin allergy assessment pathway (PAAP) initiated in primary care, is safe and effective in improving patient health outcomes and antibiotic prescribing. METHODS AND ANALYSIS: The ALABAMA trial is a multicentre, parallel-arm, open-label, randomised pragmatic trial with a nested pilot study. Adults (≥18 years) with a penicillin allergy record and who have received antibiotics in the previous 24 months will be eligible for participation. Between 1592 and 2090 participants will be recruited from participating National Health Service general practices in England. Participants will be randomised to either usual care or intervention to undergo a pre-emptive PAAP using a 1:1 allocation ratio. The primary outcome measure is the percentage of treatment response failures within 28 days of an index prescription. 2090 and 1592 participants are estimated to provide 90% and 80% power, respectively, to detect a clinically important absolute difference of 7.9% in primary outcome at 1 year between groups. The trial includes a mixed-methods process evaluation and cost-effectiveness evaluation. ETHICS AND DISSEMINATION: This trial has been approved by London Bridge Research Ethics Committee (ref: 19/LO/0176). It will be conducted in compliance with Good Clinical Practice guidelines according to the Declaration of Helsinki. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to an international, peer-reviewed journal. TRIAL REGISTRATION: ISRCTN20579216.

Expert consensus recommendations for the provision of infective endocarditis services: updated guidance from the Joint British Societies.

Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.

Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups.

A Systematic Review of the Effect of Therapeutic Drug Monitoring on Patient Health Outcomes during Treatment with Carbapenems.

Adjusting dosing regimens based on measurements of carbapenem levels may improve carbapenem exposure in patients. This systematic review aims to describe the effect carbapenem therapeutic drug monitoring (TDM) has on health outcomes, including the emergence of antimicrobial resistance (AMR). Four databases were searched for studies that reported health outcomes following adjustment to dosing regimens, according to measurements of carbapenem concentration. Bias in the studies was assessed with risk of bias analysis tools. Study characteristics and outcomes were tabulated and a narrative synthesis was performed. In total, 2 randomised controlled trials (RCTs), 17 non-randomised studies, and 19 clinical case studies were included. Significant variation in TDM practice was seen; consequently, a meta-analysis was unsuitable. Few studies assessed impacts on AMR. No significant improvement on health outcomes and no detrimental effects of carbapenem TDM were observed. Five cohort studies showed significant associations between achieving target concentrations and clinical success, including suppression of resistance. Studies in this review showed no obvious improvement in clinical outcomes when TDM is implemented. Optimisation and standardisation of carbapenem TDM practice are needed to improve intervention success and enable study synthesis. Further suitably powered studies of standardised TDM are required to assess the impact of TMD on clinical outcomes and AMR.

Diagnostic accuracy of splinter haemorrhages in patients referred for suspected infective endocarditis.

OBJECTIVE: Splinter haemorrhages are an examination finding that has classically been associated with infective endocarditis (IE), but are not included in current diagnostic algorithms. Splinter haemorrhages have not been evaluated as a diagnostic tool using modern definitions of IE. We determined their sensitivity and specificity in patients with suspected IE and investigated their inclusion in the Duke criteria. METHODS: This is a retrospective diagnostic accuracy study using data from 1119 patients with suspected IE referred to the IE service. Patients were categorised according to the Duke criteria, the current diagnostic gold standard, into Duke 'rejected', 'possible' or 'definite' groups. Definite cases (n=451) served as the true positives and rejected cases (n=486) as the true negatives against which splinter haemorrhages were compared. Duke possible cases (n=182) were used the assess the clinical impact of adding splinter haemorrhages to the Duke criteria. RESULTS: In clinically suspected cases of IE and using the Duke criteria as the gold standard comparator, splinter haemorrhages had a sensitivity of 26% (95% CI 22 to 31) (119 out of 451) and a specificity of 83% (95% CI 79 to 86) (403 out of 486). Inclusion of splinter haemorrhages as a minor vascular phenomenon in the Duke criteria would result in a reclassification of 12% of cases from Duke rejected to possible and 13% from Duke possible to definite. CONCLUSION: Splinter haemorrhages are an insensitive tool in the diagnosis of IE, but their high specificity indicates they do have clinical value in patients with suspected infection. Their inclusion in the Duke criteria as a minor vascular criterion reduces diagnostic uncertainty for some Duke possible cases, while increasing it for a similar proportion of Duke rejected cases.

Surgical Techniques and Outcomes in Patients With Intra-Cardiac Abscesses Complicating Infective Endocarditis.

Background: An intra-cardiac abscess is a serious complication of both native (NV-IE) and prosthetic valve infective endocarditis (PV-IE). Despite being an accepted indication for surgery, controversies remain regarding the optimal timing and type of operation. We aimed to report the outcomes of patients managed for intra-cardiac abscesses over more than a decade. Methods: Patients aged ≥18 years managed for intra-cardiac abscess between 1 January 2005 and 31 December 2017 were identified from a prospectively collected IE database. The primary outcome was 30-day mortality in operated patients and secondary outcomes were freedom from re-infection, re-operation and long-term mortality comparing those patients with aortic root abscess who underwent aortic valve replacement (AVR) and those who received aortic root replacement (ARR). Results: Fifty-nine patients developed an intra-cardiac abscess, and their median age was 55 (43-71) years; among them, 44 (75%) were men, and 10 (17%) were persons who injected drugs. Infection with beta-haemolytic streptococci was associated with NV-IE (p = 0.009) and coagulase-negative staphylococci with PV-IE (p = 0.005). Forty-four (75%) underwent an operation, and among those with aortic root abscess, 27 underwent AVR and 12 ARR. Thirty-day mortality was associated with infection with S. aureus (p = 0.006) but not the type or timing of the operation. Survival in operated patients was 66% at 1 year and 59% at 5 years. In operated patients, none had a relapse, although six developed late recurrence. Freedom from infection, re-operation and long-term mortality were similar in patients undergoing AVR compared to ARR. Conclusion: Patients diagnosed with intra-cardiac abscess who were not operated on had very poor survival. In those who underwent an operation, either by AVR or ARR based upon patient factors, imaging and intra-operative findings outcomes were similar.

Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms.

Staphylococcus aureus (S. aureus) is an important human pathogen and a common cause of bloodstream infection. The ability of S. aureus to form biofilms, particularly on medical devices, makes treatment difficult, as does its tendency to spread within the body and cause secondary foci of infection. Prolonged courses of intravenous antimicrobial treatment are usually required for serious S. aureus infections. This work investigates the in vitro attachment of microbubbles to S. aureus biofilms via a novel Affimer protein, AClfA1, which targets the clumping factor A (ClfA) virulence factor - a cell-wall anchored protein associated with surface attachment. Microbubbles (MBs) are micron-sized gas-filled bubbles encapsulated by a lipid, polymer, or protein monolayer or other surfactant-based material. Affimers are small (∼12 kDa) heat-stable binding proteins developed as replacements for antibodies. The binding kinetics of AClfA1 against S. aureus ClfA showed strong binding affinity (KD = 62 ± 3 nM). AClfA1 was then shown to bind S. aureus biofilms under flow conditions both as a free ligand and when bound to microparticles (polymer beads or microbubbles). Microbubbles functionalized with AClfA1 demonstrated an 8-fold increase in binding compared to microbubbles functionalized with an identical Affimer scaffold but lacking the recognition groups. Bound MBs were able to withstand flow rates of 250 µL/min. Finally, ultrasound was applied to burst the biofilm bound MBs to determine whether this would lead to biofilm biomass loss or cell death. Application of a 2.25 MHz ultrasound profile (with a peak negative pressure of 0.8 MPa and consisting of a 22-cycle sine wave, at a pulse repetition rate of 10 kHz) for 2 s to a biofilm decorated with targeted MBs, led to a 25% increase in biomass loss and a concomitant 8% increase in dead cell count. The results of this work show that Affimers can be developed to target S. aureus biofilms and that such Affimers can be attached to contrast agents such as microbubbles or polymer beads and offer potential, with some optimization, for drug-free biofilm treatment.

Impact of introducing procalcitonin testing on antibiotic usage in acute NHS hospitals during the first wave of COVID-19 in the UK: a controlled interrupted time series analysis of organization-level data.

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.

Risk of infective endocarditis after surgical and transcatheter aortic valve replacement.

OBJECTIVE: To define the incidence and risk factors for infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: All patients who underwent first SAVR or TAVI in England between 2007 and 2016 were identified from the NICOR databases. Hospital admissions with a primary diagnosis of IE were identified by linkage with the NHS Hospital Episode Statistics database. Approval was obtained from the NHS Research Ethics Committee. RESULTS: 2057 of 91 962 patients undergoing SAVR developed IE over a median follow-up of 53.9 months-an overall incidence of 4.81 [95% CI 4.61 to 5.03] per 1000 person-years. Correspondingly, 140 of 14 195 patients undergoing TAVI developed IE over a median follow-up of 24.5 months-an overall incidence of 3.57 [95% CI 3.00 to 4.21] per 1000 person-years. The cumulative incidence of IE at 60 months was higher after SAVR than after TAVI (2.4% [95% CI 2.3 to 2.5] vs 1.5% [95% CI 1.3 to 1.8], HR 1.60, p<0.001). Across the entire cohort, SAVR remained an independent predictor of IE after multivariable adjustment. Risk factors for IE included younger age, male sex, atrial fibrillation, and dialysis. CONCLUSIONS: IE is a rare complication of SAVR and TAVI. In our population, the incidence of IE was higher after SAVR than after TAVI.

Chiral nematic liquid crystal droplets as a basis for sensor systems.

For a series of phospholipid coated calamitic nematic liquid crystal droplets (5CB, 6CB, 7CB, E7 and MLC7023) of diameter ∼18 µm, the addition of chiral dopant leaves the sign of surface anchoring unchanged. Herein we report that for these chiral nematic droplets an analyte induced transition from a Frank-Pryce structure (with planar anchoring) to a nested-cup structure (with perpendicular anchoring) is accompanied by changes in the intensity of reflected light. We propose this system as both a general scheme for understanding director fields in chiral nematic liquid crystal droplets with perpendicular anchoring and as an ideal candidate to be utilised as the basis for developing cheap, single use LC-based sensor devices.

Development and randomized controlled trial of an animated film aimed at reducing behaviours for acquiring antibiotics.

BACKGROUND: Antimicrobial resistance (AMR) is a global health crisis but reducing antibiotic use can help. Some antibiotic use is driven by patient demand. OBJECTIVES: To develop an intervention to discourage antibiotic-seeking behaviour in adults. METHODS: Literature reviewed to identify behaviours for acquiring antibiotics among adults in the community. Behaviour change wheel approach was used to select the target behaviour and behaviour change techniques. An intervention in the form of a short animated film was developed and its potential impact evaluated in a randomized, controlled, online questionnaire study. RESULTS: Asking a general medical/dental practitioner for antibiotics was identified as the target behaviour. A short stop-motion animated film was chosen to deliver several behaviour-change techniques. Education and persuasion were delivered around information about the normal microbial flora, its importance for health, the negative effect of antibiotics, and about AMR. 417 UK-based individuals completed the questionnaire; median age 34.5 years, 71% female, 91% white ethnicity. 3.8% of participants viewing the test film intended to ask for antibiotics compared with 7.9% viewing the control film. Test film viewers had significantly higher knowledge scores. At 6 week follow up, knowledge scores remained significantly different, while most attitude and intention scores were not different. CONCLUSIONS: Some patients continue to ask for antibiotics. The film increased knowledge and reduced intentions to ask for antibiotics. At 6 weeks, knowledge gains remained but intentions not to ask for antibiotics had waned. Evaluation in the clinical environment, probably at the point of care, is needed to see if antibiotic prescribing can be impacted.

Use of Procalcitonin during the First Wave of COVID-19 in the Acute NHS Hospitals: A Retrospective Observational Study.

A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.

Management of penicillin allergy in primary care: a qualitative study with patients and primary care physicians.

BACKGROUND: Six percent of patients are allergic to penicillin according to their medical records. While this designation protects a small number of truly allergic patients from serious reactions, those who are incorrectly labelled may be denied access to recommended first line treatment for many infections. Removal of incorrect penicillin allergy may have positive health consequences for the individual and the general population. We aimed to explore primary care physicians' (PCPs) and patients' views and understanding of penicillin allergy with a focus on clinical management of infections in the face of a penicillin allergy record. METHODS: We conducted an interview study with 31 patients with a penicillin allergy record, and 19 PCPs in the North of England. Data were analysed thematically. RESULTS: Patients made sense of their allergy status by considering the timing and severity of symptoms. Diagnosis of penicillin allergy was reported to be 'imperfect' with PCPs relying on patient reports and incomplete medical records. PCPs and patients often suspected that an allergy record was incorrect, but PCPs were reluctant to change records. PCPs had limited knowledge of allergy services. PCPs often prescribed alternative antibiotics which were easy to identify. Both patients and PCPs differed in the extent to which they were aware of the negative consequences of incorrect penicillin allergy records, their relevance and importance to their lives, and management of penicillin allergy. CONCLUSIONS: PCPs and patients appear insufficiently aware of potential harms associated with incorrect penicillin allergy records. Some of the problems experienced by PCPs could be reduced by ensuring the details of newly diagnosed reactions to antibiotics are clearly documented. In order for PCPs to overturn more incorrect penicillin records through appropriate use of allergy services, more information and training about these services will be needed.

Production of giant unilamellar vesicles and encapsulation of lyotropic nematic liquid crystals.

We describe a modified microfluidic method for making Giant Unilamellar Vesicles (GUVs) via water/octanol-lipid/water double emulsion droplets. At a high enough lipid concentration we show that the de-wetting of the octanol from these droplets occurs spontaneously (off-chip) without the need to use shear to aid the de-wetting process. The resultant mixture of octanol droplets and GUVs can be separated by making use of the buoyancy of the octanol. A simpler microfluidic device and pump system can be employed and, because of the higher flow-rates and much higher rate of formation of the double emulsion droplets (∼1500 s-1 compared to up to ∼75 s-1), it is easier to make larger numbers of GUVs and larger volumes of solution. Because of the potential for using GUVs that incorporate lyotropic nematic liquid crystals in biosensors we have used this method to make GUVs that incorporate the nematic phases of sunset yellow and disodium chromoglycate. However, the phase behaviour of these lyotropic liquid crystals is quite sensitive to concentration and we found that there is an unexpected spread in the concentration of the contents of the GUVs obtained.

Control of Director Fields in Phospholipid-Coated Liquid Crystal Droplets.

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, phospholipids 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 synthetic 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.

Prosthetic valve endocarditis following transcatheter aortic valve implantation.

AIMS: The aims were to report the incidence and outcomes of transcatheter aortic valve implantation-infective endocarditis (TAVI-IE) from a high-volume TAVI centre in the United Kingdom, including how incidence varies relative to time from the procedure, and to assess the performance of modified Duke criteria in the diagnosis of TAVI-IE. METHODS: The retrospective, cohort study included all patients who underwent TAVI at Leeds Teaching Hospitals Trust during a 10-year period. Outcome measures were the incidence of TAVI-IE, the accuracy of the modified Duke criteria and the mortality rate. RESULTS: A total of 1337 patients were followed up for a median of 2.3 years. Thirteen patients (0.97%) were diagnosed with TAVI-IE, mean age of 81.3 years (SD 5.1 years). Four patients (30.8%) fulfilled modified Duke criteria for definite infective endocarditis. The remaining nine patients (69.2%) fulfilled the modified Duke criteria for possible infective endocarditis. In the majority (7/13; 53.8%) the causative organism was streptococcal. Cumulative incidence of TAVI-IE has risen in line with the number of patients living with TAVI prostheses, and cumulative number of TAVI-years. However, in relation to the number of 100 TAVI-years, the infection rate has remained low and static over the last 6 years. The in-hospital mortality rate was 38.5%, all attributable to TAVI-IE. CONCLUSION: The incidence of TAVI-IE was 0.97%, with an associated all-cause mortality of 53.8%. The incidence relative to the number of TAVI-years has remained low and static in recent years. The modified Duke criteria have relatively low sensitivity in the diagnosis of TAVI-IE, meaning that a high index of suspicion is required.

Long-term Outcomes Are Poor in Intravenous Drug Users Following Infective Endocarditis, Even After Surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.