A case of swine influenza A(H1N2)v in England, November 2023.

Under International Health Regulations from 2005, a human infection caused by a novel influenza A virus variant is considered an event that has potential for high public health impact and is immediately notifiable to the World Health Organisation. We here describe the clinical, epidemiological and virological features of a confirmed human case of swine influenza A(H1N2)v in England detected through community respiratory virus surveillance. Swabbing and contact tracing helped refine public health risk assessment, following this unusual and unexpected finding.

The Impact of Oral Antibiotics Prior to Cancer Diagnosis on Overall Patient Survival: Findings from an English Population-Based Cohort Study.

BACKGROUND: There is limited evidence in humans as to whether antibiotics impact the effectiveness of cancer treatments. Rodent studies have shown that disruption in gut microbiota due to antibiotics decreases cancer therapy effectiveness. We evaluated the associations between the antibiotic treatment of different time periods before cancer diagnoses and long-term mortality. METHODS: Using the Clinical Practice Research Datalink GOLD, linked to the Cancer Registry's and the Office for National Statistics' mortality records, we delineated a study cohort that involved cancer patients who were prescribed antibiotics 0-3 months; 3-24 months; or more than 24 months before cancer diagnosis. Patients' exposure to antibiotics was compared according to the recency of prescriptions and time-to-event (all-cause mortality) by applying Cox models. RESULTS: 111,260 cancer patients from England were included in the analysis. Compared with antibiotic prescriptions that were issued in the past, patients who had been prescribed antibiotics shortly before cancer diagnosis presented an increased hazard ratio (HR) for mortality. For leukaemia, the HR in the Cancer Registry was 1.32 (95% CI 1.16-1.51), for lymphoma it was 1.22 (1.08-1.36), for melanoma it was 1.28 (1.10-1.49), and for myeloma it was 1.19 (1.04-1.36). Increased HRs were observed for cancer of the uterus, bladder, and breast and ovarian and colorectal cancer. CONCLUSIONS: Antibiotics that had been issued within the three months prior to cancer diagnosis may reduce the effectiveness of chemotherapy and immunotherapy. Judicious antibiotic prescribing is needed among cancer patients.

Knowledge support for optimising antibiotic prescribing for common infections in general practices: evaluation of the effectiveness of periodic feedback, decision support during consultations and peer comparisons in a cluster randomised trial (BRIT2) - study protocol.

INTRODUCTION: This project applies a Learning Healthcare System (LHS) approach to antibiotic prescribing for common infections in primary care. The approach involves iterations of data analysis, feedback to clinicians and implementation of quality improvement activities by the clinicians. The main research question is, can a knowledge support system (KSS) intervention within an LHS implementation improve antibiotic prescribing without increasing the risk of complications? METHODS AND ANALYSIS: A pragmatic cluster randomised controlled trial will be conducted, with randomisation of at least 112 general practices in North-West England. General practices participating in the trial will be randomised to the following interventions: periodic practice-level and individual prescriber feedback using dashboards; or the same dashboards plus a KSS. Data from large databases of healthcare records are used to characterise heterogeneity in antibiotic uses, and to calculate risk scores for clinical outcomes and for the effectiveness of different treatment strategies. The results provide the baseline content for the dashboards and KSS. The KSS comprises a display within the electronic health record used during the consultation; the prescriber (general practitioner or allied health professional) will answer standard questions about the patient's presentation and will then be presented with information (eg, patient's risk of complications from the infection) to guide decision making. The KSS can generate information sheets for patients, conveyed by the clinicians during consultations. The primary outcome is the practice-level rate of antibiotic prescribing (per 1000 patients) with secondary safety outcomes. The data from practices participating in the trial and the dashboard infrastructure will be held within regional shared care record systems of the National Health Service in the UK. ETHICS AND DISSEMINATION: Approved by National Health Service Ethics Committee IRAS 290050. The research results will be published in peer-reviewed journals and also disseminated to participating clinical staff and policy and guideline developers. TRIAL REGISTRATION NUMBER: ISRCTN16230629.

Comparing antibiotic prescribing between clinicians in UK primary care: an analysis in a cohort study of eight different measures of antibiotic prescribing.

BACKGROUND: There is a need to reduce antimicrobial uses in humans. Previous studies have found variations in antibiotic (AB) prescribing between practices in primary care. This study assessed variability of AB prescribing between clinicians. METHODS: Clinical Practice Research Datalink, which collects electronic health records in primary care, was used to select anonymised clinicians providing 500+ consultations during 2012-2017. Eight measures of AB prescribing were assessed, such as overall and incidental AB prescribing, repeat AB courses and extent of risk-based prescribing. Poisson regression models with random effect for clinicians were fitted. RESULTS: 6111 clinicians from 466 general practices were included. Considerable variability between individual clinicians was found for most AB measures. For example, the rate of AB prescribing varied between 77.4 and 350.3 per 1000 consultations; percentage of repeat AB courses within 30 days ranged from 13.1% to 34.3%; predicted patient risk of hospital admission for infection-related complications in those prescribed AB ranged from 0.03% to 0.32% (5th and 95th percentiles). The adjusted relative rate between clinicians in rates of AB prescribing was 5.23. Weak correlation coefficients (<0.5) were found between most AB measures. There was considerable variability in case mix seen by clinicians. The largest potential impact to reduce AB prescribing could be around encouraging risk-based prescribing and addressing repeat issues of ABs. Reduction of repeat AB courses to prescribing habit of median clinician would save 21 813 AB prescriptions per 1000 clinicians per year. CONCLUSIONS: The wide variation seen in all measures of AB prescribing and weak correlation between them suggests that a single AB measure, such as prescribing rate, is not sufficient to underpin the optimisation of AB prescribing.

Shorter and Longer Courses of Antibiotics for Common Infections and the Association With Reductions of Infection-Related Complications Including Hospital Admissions.

BACKGROUND: Antimicrobial resistance is a serious global health concern that emphasizes completing treatment course. Recently, the effectiveness of short versus longer antibiotic courses has been questioned. This study investigated the duration of prescribed antibiotics, their effectiveness, and associated risk of infection-related complications. METHODS: Clinical Practice Research Datalink identified 4 million acute infection episodes prescribed an antibiotic in primary care between January 2014-June 2014, England. Prescriptions were categorized by duration. Risk of infection-related hospitalizations within 30 days was modelled overall and by infection type. Risk was assessed immediately after or within 30 days follow-up to measure confounders given similar and varying exposure, respectively. An interaction term with follow-up time assessed whether hazard ratios (HRs) remained parallel with different antibiotic durations. RESULTS: The duration of antibiotic courses increased over the study period (5.2-19.1%); 6-7 days were most common (66.9%). Most infection-related hospitalizations occurred with prescriptions of 8-15 days (0.21%), accompanied by greater risk of infection-related complications compared to patients who received a short prescription (HR: 1.75 [95% CI: 1.54-2.00]). Comparing HRs in the first 5 days versus remaining follow-up showed longer antibiotic courses were no more effective than shorter courses (1.02 [95% CI: 0.90-1.16] and 0.92 [95% CI: 0.75-1.12]). No variation by infection-type was observed. CONCLUSIONS: Equal effectiveness was found between shorter and longer antibiotic courses and the reduction of infection-related hospitalizations. Stewardship programs should recommend shorter courses of antibiotics for acute infections. Further research is required for treating patients with a complex medical history.SummaryPrescribing of longer courses increased over the study period. The majority of hospitalizations occurred for patients receiving longer courses. Risk of developing a complication (immediate vs remaining follow-up) found longer courses were no more effective than shorter courses.

Infection-related complications after common infection in association with new antibiotic prescribing in primary care: retrospective cohort study using linked electronic health records.

OBJECTIVE: Determine the association of incident antibiotic prescribing levels for common infections with infection-related complications and hospitalisations by comparing high with low prescribing general practitioner practices. DESIGN RETROSPECTIVE COHORT STUDY: Retrospective cohort study. DATA SOURCE: UK primary care records from the Clinical Practice Research Datalink (CPRD GOLD) and SAIL Databank (SAIL) linked with Hospital Episode Statistics (HES) data, including 546 CPRD, 346 CPRD-HES and 338 SAIL-HES practices. EXPOSURES: Initial general practice visit for one of six common infections and the proportion of antibiotic prescribing in each practice. MAIN OUTCOME MEASURES: Incidence of infection-related complications (as recorded in general practice) or infection-related hospital admission within 30 days after consultation for a common infection. RESULTS: A practice with 10.4% higher antibiotic prescribing (the IQR) was associated with a 5.7% lower rate of infection-related hospital admissions (adjusted analysis, 95% CI 3.3% to 8.0%). The association varied by infection with larger associations in hospital admissions with lower respiratory tract infection (16.1%; 95% CI 12.4% to 19.7%) and urinary tract infection (14.7%; 95% CI 7.6% to 21.1%) and smaller association in hospital admissions for upper respiratory tract infection (6.5%; 95% CI 3.5% to 9.5%) The association of antibiotic prescribing levels and hospital admission was largest in patients aged 18-39 years (8.6%; 95% CI 4.0% to 13.0%) and smallest in the elderly aged 75+ years (0.3%; 95% CI -3.4% to 3.9%). CONCLUSIONS: There is an association between lower levels of practice level antibiotic prescribing and higher infection-related hospital admissions. Indiscriminately reducing antibiotic prescribing may lead to harm. Greater focus is needed to optimise antibiotic use by reducing inappropriate antibiotic prescribing and better targeting antibiotics to patients at high risk of infection-related complications.

The Safety of Delayed Versus Immediate Antibiotic Prescribing for Upper Respiratory Tract Infections.

BACKGROUND: This study aimed to evaluate the clinical safety of delayed antibiotic prescribing for upper respiratory tract infections (URTIs), which is recommended in treatment guidelines for less severe cases. METHODS: Two population-based cohort studies used the English Clinical Practice Research Databank and Welsh Secure Anonymized Information Linkage, containing electronic health records from primary care linked to hospital admission records. Patients with URTI and prescriptions of amoxicillin, clarithromycin, doxycycline, erythromycin, or phenoxymethylpenicillin were identified. Patients were stratified according to delayed and immediate prescribing relative to URTI diagnosis. Outcome of interest was infection-related hospital admission after 30 days. RESULTS: The population included 1.82 million patients with an URTI and antibiotic prescription; 91.7% had an antibiotic at URTI diagnosis date (immediate) and 8.3% had URTI diagnosis in 1-30 days before (delayed). Delayed antibiotic prescribing was associated with a 52% increased risk of infection-related hospital admissions (adjusted hazard ratio, 1.52; 95% confidence interval, 1.43-1.62). The probability of delayed antibiotic prescribing was unrelated to predicted risks of hospital admission. Analyses of the number needed to harm showed considerable variability across different patient groups (median with delayed antibiotic prescribing, 1357; 2.5% percentile, 295; 97.5% percentile, 3366). CONCLUSIONS: This is the first large population-based study examining the safety of delayed antibiotic prescribing. Waiting to treat URTI was associated with increased risk of hospital admission, although delayed antibiotic prescribing was used similarly between high- and low-risk patients. There is a need to better target delayed antibiotic prescribing to URTI patients with lower risks of complications.

Influenza B outbreak at an adult cystic fibrosis centre - Clinical impact and factors influencing spread.

INTRODUCTION: An outbreak of Influenza B occurred at a large United Kingdom (UK) regional adult cystic fibrosis (CF) centre in May 2016. This was late in the UK 2015-2016 influenza season and occurred on a specialist ward with strict infection control procedures. This study investigates the spread of influenza, clinical consequences and potential contributing factors. METHODS: Patient records, clinical status and pulmonary function data were reviewed for all inpatients during this period. Respiratory viral PCR results, influenza vaccination status of patients and staff, and environmental factors were also recorded. Affected patients were prospectively monitored for the following three months. RESULTS: 10 of 21 inpatients developed influenza B between 5th and 12th May 2016, an attack rate of 48%. All those characterised were confirmed as the same strain of influenza B/Victoria-lineage. Influenza infection resulted in a mean FEV1 reduction of 10.5% (SD 11.3, p = 0.012), which persisted at 3 months post infection (p = 0.003). Nine of the affected cases rooms were in close proximity on the ward while patients in the two isolation rooms with enhanced ventilation did not become infected. Ventilation measurements in affected rooms ranged from 1.75 to 2.10 air changes/hour, below national recommendations. Seventy percent of affected inpatients had received the 2015/16 trivalent seasonal influenza vaccine, which did not contain a B/Victoria-lineage influenza B virus. CONCLUSION: This influenza B outbreak in CF adults had a high attack rate and a significant clinical impact. Room ventilation and a limited protection from the seasonal influenza vaccine were possible contributory factors.

Development and validation of a multivariable prediction model for infection-related complications in patients with common infections in UK primary care and the extent of risk-based prescribing of antibiotics.

BACKGROUND: Antimicrobial resistance is driven by the overuse of antibiotics. This study aimed to develop and validate clinical prediction models for the risk of infection-related hospital admission with upper respiratory infection (URTI), lower respiratory infection (LRTI) and urinary tract infection (UTI). These models were used to investigate whether there is an association between the risk of an infection-related complication and the probability of receiving an antibiotic prescription. METHODS: The study used electronic health record data from general practices contributing to the Clinical Practice Research Datalink (CPRD GOLD) and Welsh Secure Anonymised Information Linkage (SAIL), both linked to hospital records. Patients who visited their general practitioner with an incidental URTI, LRTI or UTI were included and followed for 30 days for hospitalisation due to infection-related complications. Predictors included age, gender, clinical and medication risk factors, ethnicity and socioeconomic status. Cox proportional hazards regression models were used with predicted risks independently validated in SAIL. RESULTS: The derivation and validation cohorts included 8.1 and 2.7 million patients in CPRD and SAIL, respectively. A total of 7125 (0.09%) hospital admissions occurred in CPRD and 7685 (0.28%) in SAIL. Important predictors included age and measures of comorbidity. Initial attempts at validating in SAIL (i.e. transporting the models with no adjustment) indicated the need to recalibrate the models for age and underlying incidence of infections; internal bootstrap validation of these updated models yielded C-statistics of 0.63 (LRTI), 0.69 (URTI) and 0.73 (UTI) indicating good calibration. For all three infection types, the rate of antibiotic prescribing was not associated with patients' risk of infection-related hospital admissions. CONCLUSION: The risk for infection-related hospital admissions varied substantially between patients, but prescribing of antibiotics in primary care was not associated with risk of hospitalisation due to infection-related complications. Our findings highlight the potential role of clinical prediction models to help inform decisions of prescribing of antibiotics in primary care.

The effectiveness of frequent antibiotic use in reducing the risk of infection-related hospital admissions: results from two large population-based cohorts.

BACKGROUND: Previous research reported that individuals prescribed antibiotics frequently develop antimicrobial resistance. The objective of this study was to evaluate whether frequent antibiotic use is associated with reduced hospital admissions for infection-related complications. METHODS: Population-based cohort study analysing electronic health records from primary care linked to hospital admission records. The study population included patients prescribed a systemic antibiotic, recent record of selected infections and no history of chronic obstructive pulmonary disease. Propensity-matched cohorts were identified based on quintiles of prior antibiotic use in 3 years before. RESULTS: A total of 1.8 million patients were included. Repeated antibiotic use was frequent. The highest rates of hospital admissions for infection-related complications were observed shortly after antibiotic start in all prior exposure quintiles. For patients with limited prior antibiotic use, rates then dropped quickly and substantially. In contrast, reductions over time were substantially less in patients with frequent prior antibiotic use, with rates remaining elevated over the following 6 months. In patients without comorbidity comparing the highest to lowest prior exposure quintiles in the Clinical Practice Research Databank, the IRRs were 1.18 [95% CI 0.90-1.55] in the first 3 days after prescription, 1.44 [95% CI 1.14-1.81] in the days 4-30 after and 3.22 [95% CI 2.29-4.53] in the 3-6 months after. CONCLUSIONS: Repeated courses of antibiotics, although common practice, may have limited benefit and indicator of adverse outcomes. A potential mechanism is that antibiotics may cause dysbiosis (perturbations of intestinal microbiota), contributing to colonization with resistant bacteria. Antibiotics should be used judiciously and only periodically unless indicated. Antimicrobial stewardship should include activities focusing on the substantive number of patients who repeatedly but intermittently get antibiotics.

Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne blaKPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014.

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the blaKPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of blaKPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, blaKPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of blaKPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 blaKPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of blaKPC (predominantly blaKPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), blaKPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-blaKPC and blaKPC plasmids and the common presence of multiple replicons within blaKPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control.

Human-to-Human Transmission of Monkeypox Virus, United Kingdom, October 2018.

In September 2018, monkeypox virus was transmitted from a patient to a healthcare worker in the United Kingdom. Transmission was probably through contact with contaminated bedding. Infection control precautions for contacts (vaccination, daily monitoring, staying home from work) were implemented. Of 134 potential contacts, 4 became ill; all patients survived.

Routine laboratory surveillance of antimicrobial resistance in community-acquired urinary tract infections adequately informs prescribing policy in England.

OBJECTIVES: To assess whether resistance estimates obtained from sentinel surveillance for antimicrobial resistance (AMR) in community-acquired urinary tract infections (UTIs) differ from routinely collected laboratory community UTI data. METHODS: All patients aged ≥18 years presenting to four sentinel general practices with a suspected UTI, from 13 November 2017 to 12 February 2018, were asked to provide urine specimens for culture and susceptibility. Specimens were processed at the local diagnostic laboratory. Antibiotic susceptibility testing was conducted using automated methods. We calculated the proportion of Escherichia coli isolates that were non-susceptible (according to contemporaneous EUCAST guidelines) to trimethoprim, nitrofurantoin, cefalexin, ciprofloxacin and amoxicillin/clavulanic acid, overall and by age group and sex, and compared this with routine estimates. RESULTS: Sentinel practices submitted 740 eligible specimens. The specimen submission rate had increased by 28 specimens per 1000 population per year (95% CI 21-35). Uropathogens were isolated from 23% (169/740) of specimens; 67% were E. coli (113/169). Non-susceptibility of E. coli to trimethoprim was 28.2% (95% CI 20.2-37.7) on sentinel surveillance (33.4%; 95% CI 29.5-37.6 on routine data) and to nitrofurantoin was 0.9% (95% CI 0-5.7) (1.5%; 95% CI 0.7-3.0 on routine data). CONCLUSIONS: Routine laboratory data resulted in a small overestimation in resistance (although the difference was not statistically significant) and our findings suggest that it provides an adequate estimate of non-susceptibility to key antimicrobials in community-acquired UTIs in England. This study does not support the need for ongoing local sentinel surveillance.

Antibiotic choice in UK general practice: rates and drivers of potentially inappropriate antibiotic prescribing.

OBJECTIVES: To identify the rates of potentially inappropriate antibiotic choice when prescribing for common infections in UK general practices. To examine the predictors of such prescribing and the clustering effects at the practice level. METHODS: The rates of potentially inappropriate antibiotic choice were estimated using 1 151 105 consultations for sinusitis, otitis media and externa, upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI) and urinary tract infection (UTI), using the Clinical Practice Research Datalink (CPRD). Multilevel logistic regression was used to identify the predictors of inappropriate prescribing and to quantify the clustering effect at practice level. RESULTS: The rates of potentially inappropriate prescriptions were highest for otitis externa (67.3%) and URTI (38.7%) and relatively low for otitis media (3.4%), sinusitis (2.2%), LRTI (1.5%) and UTI in adults (2.3%) and children (0.7%). Amoxicillin was the most commonly prescribed antibiotic for all respiratory tract infections, except URTI. Amoxicillin accounted for 62.3% of prescriptions for otitis externa and 34.5% of prescriptions for URTI, despite not being recommended for these conditions. A small proportion of the variation in the probability of an inappropriate choice was attributed to the clustering effect at practice level (8% for otitis externa and 23% for sinusitis). Patients with comorbidities were more likely to receive a potentially inappropriate antibiotic for URTI, LRTI and UTI in adults. Patients who received any antibiotic in the 12 months before consultation were more likely to receive a potentially inappropriate antibiotic for all conditions except otitis externa. CONCLUSIONS: Antibiotic prescribing did not always align with prescribing guidelines, especially for URTIs and otitis externa. Future interventions might target optimizing amoxicillin use in primary care.

Antibiotic prescribing for common infections in UK general practice: variability and drivers.

OBJECTIVES: To examine variations across general practices and factors associated with antibiotic prescribing for common infections in UK primary care to identify potential targets for improvement and optimization of prescribing. METHODS: Oral antibiotic prescribing for common infections was analysed using anonymized UK primary care electronic health records between 2000 and 2015 using the Clinical Practice Research Datalink (CPRD). The rate of prescribing for each condition was observed over time and mean change points were compared with national guideline updates. Any correlation between the rate of prescribing for each infectious condition was estimated within a practice. Predictors of prescribing were estimated using logistic regression in a matched patient cohort (1:1 by age, sex and calendar time). RESULTS: Over 8 million patient records were examined in 587 UK general practices. Practices varied considerably in their propensity to prescribe antibiotics and this variance increased over time. Change points in prescribing did not reflect updates to national guidelines. Prescribing levels within practices were not consistent for different infectious conditions. A history of antibiotic use significantly increased the risk of receiving a subsequent antibiotic (by 22%-48% for patients with three or more antibiotic prescriptions in the past 12 months), as did higher BMI, history of smoking and flu vaccinations. Other drivers for receiving an antibiotic varied considerably for each condition. CONCLUSIONS: Large variability in antibiotic prescribing between practices and within practices was observed. Prescribing guidelines alone do not positively influence a change in prescribing, suggesting more targeted interventions are required to optimize antibiotic prescribing in the UK.

Vaccination strategies for control of community outbreaks of hepatitis A: A comparison of two outbreaks in England.

In August 2015 two community outbreaks of hepatitis A virus (HAV) occurred in sub-urban communities in Northern England. Each was managed by an independent outbreak control team. In outbreak one, mass vaccination was deployed targeting a residential area and two schools, while in outbreak two, vaccination was reserved for household-type contacts of cases. The highest vaccination uptake was achieved in the school settings (82% and 95%). These case studies illustrate the range of approaches that can be used and the factors that influence decision-making in response to a hepatitis A community outbreak. Both outbreaks likely started from importation(s) of HAV by returning travellers and spread through extended social networks and the local community. Vaccination strategies were selected based on hypotheses about transmission pathways, which were informed by evidence from oral fluid (OF) testing of asymptomatic contacts. More evidence about the effectiveness of mass vaccination in community outbreaks of hepatitis A in low endemicity settings is needed. Hepatitis A guidelines should include recommendations for the use of mass vaccination and OF testing in outbreaks.

Relationship between prescribing of antibiotics and other medicines in primary care: a cross-sectional study.

BACKGROUND: High levels of antibiotic prescribing are a major concern as they drive antimicrobial resistance. It is currently unknown whether practices that prescribe higher levels of antibiotics also prescribe more medicines in general. AIM: To evaluate the relationship between antibiotic and general prescribing levels in primary care. DESIGN AND SETTING: Cross-sectional study in 2014-2015 of 6517 general practices in England using NHS digital practice prescribing data (NHS-DPPD) for the main study, and of 587 general practices in the UK using the Clinical Practice Research Datalink for a replication study. METHOD: Linear regression to assess determinants of antibiotic prescribing. RESULTS: NHS-DPPD practices prescribed an average of 576.1 antibiotics per 1000 patients per year (329.9 at the 5th percentile and 808.7 at the 95th percentile). The levels of prescribing of antibiotics and other medicines were strongly correlated. Practices with high levels of prescribing of other medicines (a rate of 27 159.8 at the 95th percentile) prescribed 80% more antibiotics than low-prescribing practices (rate of 8815.9 at the 5th percentile). After adjustment, NHS-DPPD practices with high prescribing of other medicines gave 60% more antibiotic prescriptions than low-prescribing practices (corresponding to higher prescribing of 276.3 antibiotics per 1000 patients per year). Prescribing of non-opioid painkillers and benzodiazepines were also strong indicators of the level of antibiotic prescribing. General prescribing levels were a much stronger driver for antibiotic prescribing than other risk factors, such as deprivation. CONCLUSION: The propensity of GPs to prescribe medications generally is an important driver for antibiotic prescribing. Interventions that aim to optimise antibiotic prescribing will need to target general prescribing behaviours, in addition to specifically targeting antibiotics.

Antibiotic prescribing patterns in general medical practices in England: Does area matter?

Antimicrobial resistance is an important public health concern. As most antibiotics are prescribed in primary care, understanding prescribing patterns in General Medical (GP) practices is vital. The aim of this study was a spatial pattern analysis of antibiotic prescribing rates in GP practices in England and to examine the association of potential clusters with area level socio-economic deprivation. The pattern analysis identified a number of hot and cold spots of antibiotic prescribing, with hot spots predominantly in the North of England. Spatial regression showed that patient catchments of hot spot practices were significantly more deprived than patient catchments of cold spot practices, especially in the domains of income, employment, education and health. This study suggests the presence of area level drivers resulting in clusters of high and low prescribing. Consequently, area level strategies may be needed for antimicrobial stewardship rather than national level strategies.

FRI-2 carbapenemase-producing Enterobacter cloacae complex in the UK.

Objectives: Detection of rarer carbapenemases is challenging, as it requires molecular assays with comprehensive coverage or the use of phenotypic methods for the detection of carbapenemase activity. We describe a new class A carbapenemase, FRI-2, in an Enterobacter cloacae complex isolate following implementation of an in-house multiplex PCR for the detection of 'rare' class A carbapenemases. Methods: MICs were determined by agar dilution. A carbapenem-resistant E. cloacae complex isolate was tested by PCR for the class A carbapenemases blaKPC, blaFRI, blaIMI, blaGES and blaSME. Carbapenemase activity was assessed using Carba NP and the carbapenem inactivation method. Whole genome and plasmid analyses of the clinical isolate and the FRI-2 transformant were performed by WGS, respectively. Typing was carried out by PFGE. Results: The E. cloacae complex isolate showed resistance to imipenem (MIC = 16 mg/L), meropenem (MIC = 8 mg/L) and ertapenem (MIC = 8 mg/L), but remained susceptible to piperacillin/tazobactam (MIC = 8 mg/L). Carbapenemase activity was confirmed in the isolate by both phenotypic methods. A blaFRI-1-like gene was detected by PCR and analysis of WGS data of the clinical isolate identified an ORF of 885 bp, which showed 97% nucleotide identity with blaFRI-1 and was named blaFRI-2. WGS of the transformant indicated blaFRI-2 was located on a 108 kb IncF/IncR plasmid. The FRI-2-positive E. cloacae complex isolate belonged to a novel ST (ST829). Conclusions: The possible circulation of rarer carbapenemases in clinical settings highlights the role of phenotypic tests to detect carbapenemase activity when molecular assays are negative for the 'big 5' carbapenemase families.

Estimating the burden of invasive and serious fungal disease in the United Kingdom.

BACKGROUND: The burden of fungal disease in the UK is unknown. Only limited data are systematically collected. We have estimated the annual burden of invasive and serious fungal disease. METHODS: We used several estimation approaches. We searched and assessed published estimates of incidence, prevalence or burden of specific conditions in various high risk groups. Studies with adequate internal and external validity allowed extrapolation to estimate current UK burden. For conditions without adequate published estimates, we sought expert advice. RESULTS: The UK population in 2011 was 63,182,000 with 18% aged under 15 and 16% over 65. The following annual burden estimates were calculated: invasive candidiasis 5142; Candida peritonitis complicating chronic ambulatory peritoneal dialysis 88; Pneumocystis pneumonia 207-587 cases, invasive aspergillosis (IA), excluding critical care patients 2901-2912, and IA in critical care patients 387-1345 patients, <100 cryptococcal meningitis cases. We estimated 178,000 (50,000-250,000) allergic bronchopulmonary aspergillosis cases in people with asthma, and 873 adults and 278 children with cystic fibrosis. Chronic pulmonary aspergillosis is estimated to affect 3600 patients, based on burden estimates post tuberculosis and in sarcoidosis. CONCLUSIONS: Uncertainty is intrinsic to most burden estimates due to diagnostic limitations, lack of national surveillance systems, few published studies and methodological limitations. The largest uncertainty surrounds IA in critical care patients. Further research is needed to produce a more robust estimate of total burden.