The impact of penicillin allergy de-labelling on the WHO AWaRe antibiotic categories: a retrospective cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: Penicillin allergy records are associated with non-Access antibiotic prescribing. Penicillin allergy de-labelling has potential to reduce non-Access antibiotic use.

'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

Factors associated with antibiotic prescribing for adults with acute conditions: an umbrella review across primary care and a systematic review focusing on primary dental care.

INTRODUCTION: One way to slow the spread of resistant bacteria is by improved stewardship of antibiotics: using them more carefully and reducing the number of prescriptions. With an estimated 7%-10% of antibiotic prescriptions globally originating from dental practices and up to 80% prescribed unnecessarily, dentistry has an important role to play. To support the design of new stewardship interventions through knowledge transfer between contexts, this study aimed to identify factors associated with the decision to prescribe antibiotics to adults presenting with acute conditions across primary care (including dentistry). METHODS: Two reviews were undertaken: an umbrella review across primary healthcare and a systematic review in dentistry. Two authors independently selected and quality assessed the included studies. Factors were identified using an inductive thematic approach and mapped to the Theoretical Domains Framework (TDF). Comparisons between dental and other settings were explored. Registration number: PROSPERO_CRD42016037174. RESULTS: Searches identified 689 publications across primary care and 432 across dental care. Included studies (nine and seven, respectively) were assessed as of variable quality. They covered 46 countries, of which 12 were low and middle-income countries (LMICs). Across the two reviews, 30 factors were identified, with 'patient/condition characteristics', 'patient influence' and 'guidelines & information' the most frequent. Two factors were unique to dental studies: 'procedure possible' and 'treatment skills'. No factor related only to LMICs. CONCLUSIONS: A comprehensive list of factors associated with antibiotic prescribing to adults with acute conditions in primary care settings around the world has been collated and should assist theory-informed design of new context-specific stewardship interventions.

Penicillin allergy de-labelling ahead of elective surgery: feasibility and barriers.

BACKGROUND: Around 10-15% of the in-patient population carry unsubstantiated 'penicillin allergy' labels, the majority incorrect when tested. These labels are associated with harm from use of broad-spectrum non-penicillin antibiotics. Current testing guidelines incorporate both skin and challenge tests; this is prohibitively expensive and time-consuming to deliver on a large scale. We aimed to establish the feasibility of a rapid access de-labelling pathway for surgical patients, using direct oral challenge. METHODS: 'Penicillin allergic' patients, recruited from a surgical pre-assessment clinic, were risk-stratified using a screening questionnaire. Patients at low risk of true, immunoglobulin E (IgE)-mediated allergy were offered direct oral challenge using incremental amoxicillin to a total dose of 500 mg. A 3-day course was completed at home. De-labelled patients were followed up to determine antibiotic use in surgery, and attitudes towards de-labelling were explored. RESULTS: Of 219 patients screened, 74 were eligible for inclusion and offered testing. We subsequently tested 56 patients; 55 were de-labelled. None had a serious reaction to the supervised challenge, or thereafter. On follow-up, 17 of 19 patients received appropriate antimicrobial prophylaxis during surgery. Only three of 33 de-labelled patients would have been happy for the label to be removed without prior specialist testing. CONCLUSION: Rapid access de-labelling, using direct oral challenge in appropriately risk-stratified patients, can be incorporated into the existing surgical care pathway. This provides immediate and potential long-term benefit for patients. Interest in testing is high among patients, and clinicians appear to follow clinic recommendations. Patients are unlikely to accept removal of their allergy label on the basis of history alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: AN17/92982.

Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC).

OBJECTIVE/BACKGROUND: The management of aortic graft infection (AGI) is highly complex and in the absence of a universally accepted case definition and evidence-based guidelines, clinical approaches and outcomes vary widely. The objective was to define precise criteria for diagnosing AGI. METHODS: A process of expert review and consensus, involving formal collaboration between vascular surgeons, infection specialists, and radiologists from several English National Health Service hospital Trusts with large vascular services (Management of Aortic Graft Infection Collaboration [MAGIC]), produced the definition. RESULTS: Diagnostic criteria from three categories were classified as major or minor. It is proposed that AGI should be suspected if a single major criterion or two or more minor criteria from different categories are present. AGI is diagnosed if there is one major plus any criterion (major or minor) from another category. (i) Clinical/surgical major criteria comprise intraoperative identification of pus around a graft and situations where direct communication between the prosthesis and a nonsterile site exists, including fistulae, exposed grafts in open wounds, and deployment of an endovascular stent-graft into an infected field (e.g., mycotic aneurysm); minor criteria are localized AGI features or fever ≥38°C, where AGI is the most likely cause. (ii) Radiological major criteria comprise increasing perigraft gas volume on serial computed tomography (CT) imaging or perigraft gas or fluid (≥7 weeks and ≥3 months, respectively) postimplantation; minor criteria include other CT features or evidence from alternative imaging techniques. (iii) Laboratory major criteria comprise isolation of microorganisms from percutaneous aspirates of perigraft fluid, explanted grafts, and other intraoperative specimens; minor criteria are positive blood cultures or elevated inflammatory indices with no alternative source. CONCLUSION: This AGI definition potentially offers a practical and consistent diagnostic standard, essential for comparing clinical management strategies, trial design, and developing evidence-based guidelines. It requires validation that is planned in a multicenter, clinical service database supported by the Vascular Society of Great Britain & Ireland.

What does NICE have to say about antimicrobial prescribing to the dental community?

Slowing the emergence of antimicrobial resistance is essential to ensuring antimicrobials remain an effective treatment for infections. Professor Dame Sally Davies, the UK Chief Medical Officer, has compared the threat posed by resistance to that from global terrorism. Antimicrobial use is a key driver of antimicrobial resistance, so reducing unnecessary prescriptions is a high priority. NICE has developed guidance aimed at optimising prescribing within publically-funded health and care services. With primary care dentists responsible for 5% of all NHS antibacterial prescriptions, the dental community has a role to play in guarding the effectiveness of antibacterial drugs. This article describes three recent NICE publications that have implications for dentists. Antimicrobial Stewardship: Systems and Processes (NG 15) is an overarching guideline for the NHS aimed at commissioners and providers of health and care services, together with more specific guidance for prescribers. Prophylaxis against infective endocarditis (CG64) was reissued in 2015 following a review of the latest evidence prompted by concerns that the incidence of infective endocarditis had increased since initial publication of CG64 in 2008. Changing risk-related behaviours of the public in relation to expectations for antimicrobial prescriptions is currently in production (PHG89) . This paper outlines the key recommendations from these NICE guidelines as they relate to the dental community.

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations.

Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.

What is the effect of penicillin dosing interval on outcomes in streptococcal infective endocarditis?

OBJECTIVES: Penicillin is an important treatment option for streptococcal infective endocarditis (IE), but its short half-life requires frequent re-dosing (4- or 6-hourly). There is a variation between the dosing regimens in different guidelines and consequent differences in the dosing interval. The objective of this study was to examine the relationship between the penicillin dosing interval and outcomes in streptococcal IE. METHODS: A retrospective study of cases of streptococcal IE was undertaken using the Leeds Endocarditis Service database. Cases were included if the first-line therapy had been penicillin and excluded if patients had received less than 72 h of therapy. Details of antimicrobial therapy and outcomes were collated using strict definitions. Various parameters were considered as independent variables in a multivariate logistic regression analysis. Univariate analysis of categorical data was carried out using a χ(2) test, and analysis of continuous data using an unpaired t-test. RESULTS: Two hundred and twelve cases were included in the final analysis. Of the parameters considered, a 4-hourly dosing interval [unadjusted OR = 2.79 (95% CI 1.43-5.62)] and initial echocardiographic evidence of abscess or severe valve regurgitation [unadjusted OR = 0.30 (95% CI 0.13-0.66)] were the only statistically significant factors associated with the success or failure of penicillin therapy. The odds of a successful outcome were almost three times greater with a 4-hourly regimen than with a 6-hourly regimen. Failure of penicillin therapy had no correlation with the MIC of penicillin or the concurrent administration of gentamicin. CONCLUSIONS: Penicillin continues to be an effective therapy for IE. This study suggests that a 4-hourly dosing interval may be relevant in predicting the success of initial medical therapy. Further prospective studies are warranted to evaluate relationships in more detail.

NICE guidance on antibiotic prophylaxis to prevent infective endocarditis: a survey of clinicians' attitudes.

BACKGROUND: Since the introduction of the National Institute for Health and Clinical Excellence (NICE) guideline (CG064) in 2008 recommending cessation of antibiotic prophylaxis (AP) against infective endocarditis (IE), low level prescribing persists in the UK and is a potential reason why there has been no significant change in the general upward trend in cases of IE. AIM: To undertake a survey of dentists (Ds), cardiologists and cardiothoracic surgeons (C/CTSs) and infection specialists (ISs) to determine why this might be the case. DESIGN: Internet questionnaire-based survey. METHODS: A questionnaire was distributed by email to specialists via UK national societies. RESULTS: A total of 1168 responses were received. All the specialist groups are aware of the guideline (99%). Ds are broadly satisfied, whereas C/CTSs are not. Most Ds follow the NICE guidance (87%), whereas many C/CTSs (39%) do not; ISs adopt a middle course (56%). Even amongst Ds, a significant proportion believe that patients with a prosthetic heart valve (25%) or previous history of IE (38%) should receive AP. A total of 36% of Ds have prescribed AP since March 2008 and many have undertaken procedures where AP has been prescribed by someone else. The majority of respondents (65%) feel that more evidence is required, preferably in the form of a randomized controlled trial. CONCLUSION: Many patients perceived to be at high risk of IE are still receiving AP in conflict with current NICE guidance.

Vascular access strategy for delivering long-term antimicrobials to patients with infective endocarditis: device type, risk of infection and mortality.

BACKGROUND: This paper reports the use of different vascular access devices and the incidence of intravascular catheter-related infection (CRI) in patients receiving intravenous antibiotics for infective endocarditis (IE). AIM: To examine whether rates of infection vary with type of vascular access device, and assess the impact of CRI on mortality in IE. METHODS: A prospective observational service evaluation of all inpatients who received intravenous antibiotics for IE was performed. In total, 114 inpatients were evaluated. All cases of CRI [including exit-site infection, intravascular catheter-related bloodstream infection (CRBSI) and mortality] were recorded. Tunnelled and non-tunnelled central venous catheters (CVCs), and peripherally inserted cannulae were used for antibiotic delivery. FINDINGS: There were 15 episodes of CRI, 11 of which were CRBSI (all associated with CVC use). The remainder comprised uncomplicated exit-site infections. Use of tunnelled CVCs [hazard ratio (HR) 16.95, 95% confidence interval (CI) 2.13-134.93; P = 0.007] and non-tunnelled CVCs (HR 24.54, 95% CI 2.83-212.55; P = 0.004) was associated with a significantly increased risk of CRI. Risk of mortality increased significantly with Staphylococcus aureus as the cause of IE (P < 0.001) and CRBSI (P = 0.034). CONCLUSION: Risk of CRI in patients with IE is linked to the type of vascular access device used. Rates of CRBSI were greatest with CVCs, while peripheral venous cannulae were not associated with CRBSI or serious sequelae. Many patients (40%) tolerated complete treatment courses delivered via peripheral cannulae. These findings confirm the importance of device selection in reducing the risk of CRI; a potentially modifiable variable that impacts on outcome and mortality in IE.

Late-onset prosthetic valve endocarditis caused by Mycoplasma hominis, diagnosed using broad-range bacterial PCR.

We report what is believed to be the first case of late-onset prosthetic valve endocarditis caused by Mycoplasma hominis in a case of blood culture-negative endocarditis. The objective of this report is to emphasize the use of a broad-range PCR technique for bacterial 16S rRNA genes in identifying the causative pathogen, thus enabling targeted antimicrobial treatment.

Potential for aerosolization of Clostridium difficile after flushing toilets: the role of toilet lids in reducing environmental contamination risk.

BACKGROUND: Toilet facilities in healthcare settings vary widely, but patient toilets are commonly shared and do not have lids. When a toilet is flushed without the lid closed, aerosol production may lead to surface contamination within the toilet environment. AIM: To substantiate the risks of airborne dissemination of C. difficile following flushing a toilet, in particular when lids are not fitted. METHODS: We performed in-situ testing, using faecal suspensions of C. difficile to simulate the bacterial burden found during disease, to measure C. difficile aerosolization. We also measured the extent of splashing occurring during flushing of two different toilet types commonly used in hospitals. FINDINGS: C. difficile was recoverable from air sampled at heights up to 25 cm above the toilet seat. The highest numbers of C. difficile were recovered from air sampled immediately following flushing, and then declined 8-fold after 60 min and a further 3-fold after 90 min. Surface contamination with C. difficile occurred within 90 min after flushing, demonstrating that relatively large droplets are released which then contaminate the immediate environment. The mean numbers of droplets emitted upon flushing by the lidless toilets in clinical areas were 15-47, depending on design. C. difficile aerosolization and surrounding environmental contamination occur when a lidless toilet is flushed. CONCLUSION: Lidless conventional toilets increase the risk of C. difficile environmental contamination, and we suggest that their use is discouraged, particularly in settings where CDI is common.

The MRI appearances of early vertebral osteomyelitis and discitis.

AIM: To describe the magnetic resonance imaging (MRI) appearances in patients with a clinical history suggestive of vertebral osteomyelitis and discitis who underwent MRI very early in their clinical course. MATERIALS AND METHODS: A retrospective review of the database of spinal infections from a spinal microbiological liaison team was performed over a 2 year period to identify cases with clinical features suggestive of spinal infection and an MRI that did not show features typical of vertebral osteomyelitis and discitis. All patients had positive microbiology and a follow up MRI showing typical features of spinal infection. RESULTS: In four cases the features typical of spinal infection were not evident at the initial MRI. In three cases there was very subtle endplate oedema associated with disc degeneration, which was interpreted as Modic type I degenerative endplate change. Intravenous antibiotic therapy was continued prior to repeat MRI examinations. The mean time to the repeat examination was 17 days with a range of 8-22 days. The second examinations clearly demonstrated vertebral osteomyelitis and discitis. CONCLUSION: Although MRI is the imaging method of choice for vertebral osteomyelitis and discitis in the early stages, it may show subtle, non-specific endplate subchondral changes; a repeat examination may be required to show the typical features.

Examination of tunnelled haemodialysis catheters using scanning electron microscopy.

Tunnelled haemodialysis catheters (t-HDC) are prone to colonization by microorganisms, resulting in increased morbidity and mortality. A previous study concluded that all culture-negative catheters removed from cancer patients were colonized by microbial biofilms when examined by scanning electron microscopy (SEM). Examination of t-HDC by SEM has not been published before. A total of 44 segments (0.5 cm each) from 11 ex-vivo t-HDC were examined by SEM prior to endoluminal brushing and quantitative culture to determine their colonization status. Endoluminal brushing yielded a positive culture from two catheters. Methicillin-sensitive Staphylococcus aureus was grown from one catheter and a Streptococcus species was cultured from the second. SEM examination revealed universal endoluminal coverage by adherent biological material (ABM), which was composed of fibrin, platelets and other host-derived products. However, bacterial cells were visible on the two culture-positive catheters and on two out of nine culture-negative catheters, and were possibly present on one culture-negative catheter. In conclusion, in this study the prevalence of microbial colonization of ex vivo t-HDC was 18% using the endoluminal brushing technique and 36% when examined by SEM. The previously reported universal microbial colonization of central venous catheters is likely to represent coverage by ABM rather than by microbial biofilms.

Use of multilocus sequence typing for the investigation of colonisation by Candida albicans in intensive care unit patients.

A prospective study was performed to determine the prevalence of candidal colonisation on the general intensive care unit at a large teaching hospital. Colonisation with Candida spp. was found to be common, occurring in 79% of patients on the unit. C. albicans was the commonest species, colonising 64% of patients, followed by C. glabrata (18%) and C. parapsilosis (14%). Most of the members of staff tested carried Candida spp. at some point, although carriage appeared to be transient. C. parapsilosis was the most commonly isolated species from staff hands, whereas C. albicans was the most commonly isolated species from the mouth. The molecular epidemiology of C. albicans was investigated using Ca3 typing and multilocus sequence typing (MLST). MLST proved to be a reproducible typing method and a useful tool for the investigation of the molecular epidemiology of C. albicans. The results of the molecular typing provided evidence for the presence of an endemic strain on the unit, which was isolated repeatedly from patients and staff. This finding suggests horizontal transmission of C. albicans on the unit though it may also reflect the relative frequency of C. albicans strain types colonising patients on admission. This study has important implications for the epidemiology of systemic candidal infections.

Paediatric neck abscesses: microbiology and management.

INTRODUCTION: Paediatric neck abscesses remain common problems which are sometimes difficult to manage. METHODS AND MATERIALS: We conducted a retrospective study of 64 children who underwent incision and drainage of neck abscesses at Leeds General Infirmary from 1 February 2002 to 31 July 2006. The aim of this study was to identify the presenting symptoms in children, the appropriateness of prescribed antibiotics and the role of atypical mycobacteria in neck infections. The outcome measure was clinical resolution of the abscess. RESULTS: The mean presenting age was 44.2 months (3.68 years). The commonest sign and symptom was neck mass (96.9 per cent). The mean period of hospitalisation was 3.7 (+/- standard deviation of 1.9) days. Staphylococcus aureus (48.4 per cent) was the commonest organism cultured. Atypical mycobacteria were found in only 4.7 per cent of the specimens. Flucloxacillin was the most common antibiotic used (57.8 per cent), often in combination with other antimicrobials. The abscess recurrence rate was 4.7 per cent. No fatalities occurred in this series of patients. CONCLUSION: Appropriately prescribed intravenous antibiotics and surgical drainage remain the central core of treatment. Atypical mycobacterial infection is an important differential diagnosis of a painless, cervico-facial mass. An algorithm for the management of paediatric neck abscesses is proposed.

Invasive Cryptococcus neoformans infection in an asplenic patient.

Individuals who are asplenic or have impaired splenic function are at increased risk of developing life-threatening infections, especially due to encapsulated bacteria. This risk is higher in children, but adults can also develop fulminant infection or "post splenectomy sepsis" (PSS). Cryptococcus neoformans is an encapsulated yeast usually causing infection in immunocompromised patients. In a recent review of cryptococcal infection in HIV-negative patients, splenectomy was reported to be a risk factor for infection in 3% of cases. Detailed case reports are lacking. Here we report a case of disseminated C. neoformans infection in a patient who had a splenectomy performed for warm autoantibody haemolytic anaemia some months before he presented with signs and symptoms of meningitis. This report aims to raise awareness of the possibility of C. neoformans infection in asplenic patients.

Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy.

These guidelines have been produced following a literature review of the requirement for prophylaxis to prevent bacterial endocarditis following dental and surgical interventions. Recommendations are made based on the quality of available evidence and the consequent risk of morbidity and mortality for "at risk" patients.