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Increases in invasive group A streptococcal (iGAS) infection and associated deaths, particularly in children, above seasonally expected levels are being seen this season (772 notifications reported in weeks 37 to 48 in 2022) across England. Diagnoses of iGAS infection from lower respiratory tract specimens in children under 15 years increased to 28% in November 2022. Medical practitioners have been alerted to the exceptional increase in incidence, including unusual numbers of children presenting with pulmonary empyema.

Vaccines are a key part of the global strategy to tackle antimicrobial resistance (AMR) since prevention of infection should reduce antibiotic use. England commenced national rollout of a live attenuated influenza vaccine (LAIV) programme for children aged 2-3 years together with a series of geographically discrete pilot areas for primary school age children in 2013 extending to older children in subsequent seasons. We investigated vaccine programme impact on community antibiotic prescribing rates. Antibiotic prescribing incidence rates for respiratory (RTI) and urinary tract infections (UTI; controls) were calculated at general practice (GP) level by age category (children

ObjectiveTo estimate the incidence of laboratory-confirmed, invasive bacterial infections (IBIs) by week of age in infants over a 7-year period.DesignAnalysis of prospective national surveillance data for England.SettingNational Health Service hospitals in England.PatientsInfants aged Main outcome measuresIBI incidence by week of age, incidence rate ratio (IRR) at 8, 12 and 16 weeks compared with the first week of life, and the main pathogens responsible for IBI.ResultsThere were 22 075 IBI episodes between 2010/2011 and 2016/2017. The lowest annual cases were in 2011/2012 (n=2 799; incidence, 412/100 000 population), increasing year-on-year to 3 698 cases in 2016/2017 (incidence, 552/100 000 population). The incidence was highest in the first week of life and then declined rapidly. In 2016/2017, compared with the first week of life, weekly IBI incidence was 92% lower at 8 weeks (IRR 0.08; 95% CI 0.06 to 0.10) and 96% lower at 16 weeks of age (IRR 0.04; 95% CI 0.03 to 0.06). In 2016/2017, Escherichia coli was the most prevalent pathogen responsible for IBI (n=592, 16.0%), followed by group B Streptococci (n=493, 13.3%), Staphylococcus aureus (n=400, 10.8%) and Enterococci (n=304, 8.2%). The other pathogens were individually responsible for ConclusionIBI incidence declines rapidly after the first week of life, such that infants have a very low risk of IBI by the time they are eligible for their routine immunisations from 8 weeks of age.

IntroductionAntibiotic resistance poses a threat to public health and healthcare systems. Escherichia coli causes more bacteraemia episodes in England than any other bacterial species. This study aimed to estimate the burden of E. coli bacteraemia and associated antibiotic resistance in the secondary care setting.Materials and methodsThis was a retrospective cohort study, with E. coli bacteraemia as the main exposure of interest. Adult hospital in-patients, admitted to acute NHS hospitals between July 2011 and June 2012 were included. English national surveillance and administrative datasets were utilised. Cox proportional hazard, subdistribution hazard and multistate models were constructed to estimate rate of discharge, rate of in-hospital death and excess length of stay, with a unit bed day cost applied to the latter to estimate cost burden from the healthcare system perspective.Results14,042 E. coli bacteraemia and 8,919,284 non-infected inpatient observations were included. E. coli bacteraemia was associated with an increased rate of in-hospital death across all models, with an adjusted subdistribution hazard ratio of 5.88 (95% CI: 5.62-6.15). Resistance was not found to be associated with in-hospital mortality once adjusting for patient and hospital covariates. However, resistance was found to be associated with an increased excess length of stay. This was especially true for third generation cephalosporin (1.58 days excess length of stay, 95% CI: 0.84-2.31) and piperacillin/tazobactam resistance (1.23 days (95% CI: 0.50-1.95)). The annual cost of E. coli bacteraemia was estimated to be 14,346,400 pound (2012 ) pound, with third-generation cephalosporin resistance associated with excess costs per infection of 420 pound (95% CI: 220-630).ConclusionsE. coli bacteraemia places a statistically significant burden on patient health and the hospital sector in England. Resistance to front-line antibiotics increases length of stay; increasing the cost burden of such infections in the secondary care setting.

Objectives: To evaluate the association between use of different antibiotics and trimethoprim resistance at the population level.Methods: Monthly primary care prescribing data were obtained from NHS Digital. Positive Enterobacteriaceae records from urine samples from patients between April 2014 and January 2016 in England were extracted from PHE's Second Generation Surveillance System (SGSS). Elastic net regularization and generalized boosted regression models were used to evaluate associations between antibiotic prescribing and trimethoprim resistance, both measured at Clinical Commission Group level.Results: In total, 2 487 635 (99%) of 2 513 285 urine Enterobacteriaceae samples from 1 667 839 patients were tested for trimethoprim resistance. Using both elastic net regularization and generalized boosted regression models, geographical variation in trimethoprim resistance among Enterobacteriaceae urinary samples could be partly explained by geographical variation in use of trimethoprim (relative risk = 1.14, 95% CI = 1.02-1.75; relative influence = 4.1) and penicillins with extended spectrum (mainly amoxicillin/ampicillin in England) (relative risk = 1.19, 95% CI = 1.11-1.30; relative influence = 7.4). Nitrofurantoin use was associated with lower trimethoprim resistance levels (relative risk = 0.83, 95% CI = 0.57-0.96; relative influence = 9.2).Conclusions: Use of amoxicillin/ampicillin explained more of the variance in trimethoprim resistance than trimethoprim use, suggesting that co-selection by these antibiotics is an important driver of trimethoprim resistance levels at the population level. Nitrofurantoin use was consistently associated with lower trimethoprim resistance levels, indicating that trimethoprim resistance levels could be lowered if trimethoprim use is replaced by nitrofurantoin.

Hospital networks, formed by patients visiting multiple hospitals, affect the spread of hospital-associated infections, resulting in differences in risks for hospitals depending on their network position. These networks are increasingly used to inform strategies to prevent and control the spread of hospital-associated pathogens. However, many studies only consider patients that are received directly from the initial hospital, without considering the effect of indirect trajectories through the network. We determine the optimal way to measure the distance between hospitals within the network, by reconstructing the English hospital network based on shared patients in 2014–2015, and simulating the spread of a hospital-associated pathogen between hospitals, taking into consideration that each intermediate hospital conveys a delay in the further spread of the pathogen. While the risk of transferring a hospital-associated pathogen between directly neighbouring hospitals is a direct reflection of the number of shared patients, the distance between two hospitals far-away in the network is determined largely by the number of intermediate hospitals in the network. Because the network is dense, most long distance transmission chains in fact involve only few intermediate steps, spreading along the many weak links. The dense connectivity of hospital networks, together with a strong regional structure, causes hospital-associated pathogens to spread from the initial outbreak in a two-step process: first, the directly surrounding hospitals are affected through the strong connections, second all other hospitals receive introductions through the multitude of weaker links. Although the strong connections matter for local spread, weak links in the network can offer ideal routes for hospital-associated pathogens to travel further faster. This hold important implications for infection prevention and control efforts: if a local outbreak is not controlled in time, colonised patients will appear in other regions, irrespective of the distance to the initial outbreak, making import screening ever more difficult., Author summary Shared patients can spread hospital-associated pathogens between hospitals, together forming a large network in which all hospitals are connected. We set out to measure the distance between hospitals in such a network, best reflecting the risk of a hospital-associated pathogen spreading from one to the other. The central problem is that this risk may not be a directly reflected by the weight of the direct connections between hospitals, because the pathogen could arrive through a longer indirect route, first causing a problem in an intermediate hospital. We determined the optimal balance between connection weights and path length, by testing different weighting factors between them against simulated spread of a pathogen. We found that while strong connections are important risk factor for a hospital’s direct neighbours, weak connections offer ideal indirect routes for hospital-associated pathogens to travel further faster. These routes should not be underestimated when designing control strategies.

After decades of decreasing scarlet fever incidence, a dramatic increase was seen in England beginning in 2014. Investigations were launched to assess clinical and epidemiological patterns and identify potential causes.In this population-based surveillance study, we analysed statutory scarlet fever notifications held by Public Health England from 1911 to 2016 in England and Wales to identify periods of sudden escalation of scarlet fever. Characteristics of cases and outbreaks in England including frequency of complications and hospital admissions were assessed and compared with the pre-upsurge period. Isolates from throat swabs were obtained and were emm typed.Data were retrieved for our analysis between Jan 1, 1911, and Dec 31, 2016. Population rates of scarlet fever increased by a factor of three between 2013 and 2014 from 8·2 to 27·2 per 100 000 (rate ratio [RR] 3·34, 95% CI 3·23-3·45; p0·0001); further increases were observed in 2015 (30·6 per 100 000) and in 2016 (33·2 per 100 000), which reached the highest number of cases (19 206) and rate of scarlet fever notifcation since 1967. The median age of cases in 2014 was 4 years (IQR 3-7) with an incidence of 186 per 100 000 children under age 10 years. All parts of England saw an increase in incidence, with 620 outbreaks reported in 2016. Hospital admissions for scarlet fever increased by 97% between 2013 and 2016; one in 40 cases were admitted for management of the condition or potential complications. Analysis of strains (n=303) identified a diversity of emm types with emm3 (43%), emm12 (15%), emm1 (11%), and emm4 (9%) being the most common. Longitudinal analysis identified 4-yearly periodicity in population incidence of scarlet fever but of consistently lower magnitude than the current escalation.England is experiencing an unprecedented rise in scarlet fever with the highest incidence for nearly 50 years. Reasons for this escalation are unclear and identifying these remains a public health priority.None.

BackgroundAntibiotic resistance poses a threat to public health and a burden to healthcare systems. Escherichia coli causes more bacteraemia cases in England than any other bacterial species, these infections, in part due to their high incidence, also pose a significant antibiotic resistance burden. The main aim of this study was to estimate the impact of E. coli bacteraemia on patient in-hospital mortality and length of stay. Secondarily, this study also aimed to estimate the effect of antibiotic resistance on these outcomes.Methods and FindingsCase patients were adult E. coli bacteraemia patients infected between July 2011 and June 2012, as reported in an English national mandatory surveillance database, with susceptibility data taken from a national laboratory surveillance database. Control patients were all non-case, adult patients with an English hospital admission record. Case and control patient characteristics and admission information were taken from NHS Digital Datasets. ‘Resistance’ was defined as non-susceptible and intermediate isolates, whilst ‘susceptible’ was defined as susceptible and non-tested isolates. Time to in-hospital mortality and discharge was investigated through Cox proportional hazards models. To acquire estimates of excess length of stay, multistate models were constructed, with a unit bed day cost applied to estimate cost burden. The total number of case and control hospital spells was 14,051 and 8,919,275 respectively. Acquisition of E. coli bacteraemia was associated with a statistically significant increased daily risk of in-hospital mortality, especially for the first eight days of someone’s hospital admission [Hazard Ratio = 2.77 (95% confidence interval; 2.61-2.94)]. Antibiotic resistance did not seem to significantly increase this risk further, though did significantly reduce risk of experiencing a discharge event (dead or alive). E.coli bacteraemia was estimated to cost £14,340,900 over the study period (rounded to the nearest £100), with resistance associated with excess costs per infection of £220 - £420 dependent on resistance type, for those where a significant impact was found (rounded to the nearest £10).ConclusionsE. coli bacteraemia places a significant burden on patient health and on the hospital sector in England. Resistance is an important factor on length of stay with regards to such infections.

BACKGROUND Bacterial meningitis remains a major cause of morbidity and mortality in young infants. Understanding the epidemiology and burden of disease is important. METHODS Prospective, enhanced, national population-based active surveillance was undertaken to determine the incidence, etiology, and outcome of bacterial meningitis in infants aged

Hospital performance is often measured using self-reported statistics, such as the incidence of hospital-transmitted micro-organisms or those exhibiting antimicrobial resistance (AMR), encouraging hospitals with high levels to improve their performance. However, hospitals that increase screening efforts will appear to have a higher incidence and perform poorly, undermining comparison between hospitals and disincentivising testing, thus hampering infection control. We propose a surveillance system in which hospitals test patients previously discharged from other hospitals and report observed cases. Using NHS Hospital Episode Statistics data, we analysed patient movements across England and assessed the number of hospitals required to participate in such a reporting scheme to deliver robust estimates of incidence. With over 1.2 million admissions to English hospitals previously discharged from other hospitals annually, even when only a fraction of hospitals (41/155) participate (each screening at least 1000 of these admissions), the proposed surveillance system can estimate incidence across all hospitals. By reporting on other hospitals, the reporting of incidence is separated from the task of improving own performance. Therefore the incentives for increasing performance can be aligned to increase (rather than decrease) screening efforts, thus delivering both more comparable figures on the AMR problems across hospitals and improving infection control efforts.

The provision of better access to and use of surveillance data is a key component of the UK 5 Year Antimicrobial Resistance (AMR) Strategy. Since April 2016, PHE has made data on practice (infection prevention and control; antimicrobial stewardship) and outcome (prevalence of AMR, antibiotic use and healthcare-associated infections) available through Fingertips, a publicly accessible web tool (https://fingertips.phe.org.uk/profile/amr-local-indicators). Fingertips provides access to a wide range of public health data presented as thematic profiles, with the above data being available through the 'AMR local indicators' profile. Local data on a range of indicators can be viewed at the level of National Health Service acute trusts, Clinical Commissioning Groups or general practitioner practices, all of which can be compared with the corresponding aggregate values for England to allow benchmarking. The data can be viewed in a range of formats including an overview showing counts and rates, interactive maps, spine charts and graphs that show temporal trends over a range of time scales or allow correlations between pairs of indicators. The aim of the AMR local indicators profile on Fingertips is to support the development of local action plans to optimize antibiotic prescribing and reduce AMR and healthcare-associated infections. Provision of access to relevant information in an easy to use format will help local stakeholders, including healthcare staff, commissioners, Directors of Public Health, academics and the public, to benchmark relevant local AMR data and to monitor the impact of local initiatives to tackle AMR over time.

BACKGROUND: Hospital-acquired bloodstream infection (HA-BSI) requires immediate effective antibiotic treatment. However, there are no published national data for England that describe the pathogen profile and antibiotic resistance rates of HA-BSI in children. METHODS: Probabilistic matching methods were used to link national data on microbiologically confirmed BSI to hospital in-patient admissions data for the period of January 2009-March 2010. HA-BSI was defined as a positive blood culture drawn from a child aged 1 month-18 years 2 or more days after admission (and before discharge). RESULTS: A total of 8718 episodes of BSI was reported during the study period. Linkage allowed 82% of records to be matched, of which 23% (1734) were HA-BSI, giving a rate of 4.74 per 1000 admissions. The median age of infection was 1 year, and 54% of infections were in males. Methicillin resistance was seen in 83% and 17% of coagulase-negative staphylococci and Staphylococcus aureus, respectively. Penicillin resistance was rare in pyogenic streptococci but more common in viridans streptococci (39%). Among Gram-positive organisms, only 3% were vancomycin-resistant. The overall proportion of Gram-negative bacteria resistant to recommended empirical antibiotics (meropenem or piperacillin/tazobactam) was 5% and 16%, respectively, but

Background. Hospital-acquired bloodstream infection (HA-BSI) is associated with substantial morbidity, mortality, and healthcare costs in all patient populations. Young children have been shown to have a high rate of healthcare-associated infections compared with the adult population. We aimed to quantify the excess mortality and length of stay in pediatric patients from HA-BSI. Methods. We analyzed data collected retrospectively from a probabilistically linked national database of pediatric (aged 1 month–18 years) in-patients with a microbiologically confirmed HA-BSI in England between January and March 2009. A time-dependent Cox regression model was fit to determine the presence of any effect. Furthermore, a multistate model, adjusted for the time to onset of HA-BSI, was used to compare outcomes in patients with HA-BSI to thosewithout HA-BSI. We furtheradjusted for patients’ characteristics as recorded in hospital admission data. Results. The dataset comprised 333 605 patients, with 214 cases of HA-BSI. After adjustment for time to HA-BSI and comorbidities, the hazard for discharge (dead or alive) from hospital for patients with HA-BSI was 0.9 times (95% confidence interval [CI], .8–1.1) that of noninfected patients. Excess length of stay associated with all-cause HA-BSI was 1.6 days (95% CI, .2–3.0), although this duration varied by pathogen. Patients with HA-BSI had a 3.6 (95% CI, 1.3–10.4) times higher hazard for in-hospital death than noninfected patients. Conclusions. Hospital-acquired bloodstream infection increased the length of stay and mortality of pediatric inpatients. The results of this study provide an evidence base to judge the health and economic impact of programs to prevent and control HA-BSI in children.

Between 1998 and 2000, 95.6% of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemias in the UK were due to two epidemic strains, namely EMRSA-15 or EMRSA-16 (60.2% and 35.4%, respectively). We sought to determine the proportions of these strains before and after the general decline in MRSA bacteraemia that began around 2004.Consecutive MRSA isolates collected in 2001, 2003, 2005 and 2007 by the BSAC Bacteraemia Surveillance Programme were categorized to multilocus sequence typing (MLST) clonal complex and to SCCmec type by PCR. MICs were determined by the BSAC method. Data trends were tested for significance using a generalized linear regression model.Collectively, EMRSA-15 and EMRSA-16 consistently accounted for approximately 95% of MRSA studied between 2001 and 2007, but the proportions of EMRSA-16 declined from 21.4% in 2001 to 9% in 2007 (P0.05), whilst the proportion of EMRSA-15 rose commensurately, accounting for 85% of MRSA in 2007. Ciprofloxacin and erythromycin resistance were common amongst both EMRSA-15 and EMRSA-16.EMRSA-15 and EMRSA-16 remain the main MRSA strains in bacteraemia in the UK, but the proportion of EMRSA-16 declined from the late 1990 s, thus preceding the general decline in MRSA bacteraemias that began in the middle of the present decade.

Bacteraemia in children is a potentially life-threatening condition. The objective of this study was to determine trends in the aetiology of bacteraemia in children aged 1 month–15 years in England and Wales by collecting data voluntarily reported by National Health Service hospital microbiology laboratories. Over the 10-year period 1998–2007, a total of 51 788 bacteraemia cases involving 105 genera/species of bacteria were reported. Total annual reports of bacteraemia increased from 4125 to 6916, with a mean increase of 6.5 % per year (95 % CI: 1.3–12.1 %). In 2007, just over half the cases were accounted for by four groups of organisms: coagulase-negative staphylococci (28 %), Staphylococcus aureus (10 %), non-pyogenic streptococci (9 %) and Streptococcus pneumoniae (7 %). These organisms along with a further 13 species/genera accounted for 90 % of the cases. The commonest Gram-negative organisms were Neisseria meningitidis and Escherichia coli, which each accounted for 5 % of total bacteraemia reports in 2007. There was a significant decrease in reports of bacteraemia due to the three vaccine-preventable pathogens Haemophilus influenzae, N. meningitidis and Strep. pneumoniae, following the introduction of each vaccine programme or catch-up campaign. This study identified the commonest causes of bacteraemia in children in England and Wales, and highlighted the shifts in trends observed over time.

Background and aims Meningitis in the first 3 months of life is associated with significant mortality and morbidity. Previous UK studies were conducted in the 1980s and 1990s. It is important to define the current burden of disease in order to prioritise treatment and prevention strategies. Methods Cases were identified prospectively by active surveillance through the British Paediatric Surveillance Unit, routine microbiological surveillance through the Health Protection Agency and via parents of cases through meningitis and Group B streptococcus (GBS) support charities. The surveillance period was July 2010 – July 2011. Results 365 cases were identified, equivalent to a total incidence of 0.38/1000 live-births (95% CI: 0.35- 0.42); for late-onset (n = 252) was 0·27 per 1000 (0·23—0·30), and for early-onset (n = 113) was 0·12 per 1000 (0·10—0·14). The male to female ratio was 1.3:1. The median age of disease (IQR) was 14 days (3–36). The majority of cases (62%) were admitted from home. Lumbar puncture was performed in 319/329 (97%) of the cases. The timing of LP was available in 307 (96%) and was before the first dose of antibiotics in only 110/306 (36%) of the cases. Of the 304 organisms isolated 151 (50%) were Group B Streptococcus (GBS), 40 (13%) E coli , 28 (9%) Streptococcus pneumoniae (SPn), 24 (8%) Meningococcus, 11 (4%) Listeria monocytogenes , 24 (8%) other Gram positive bacteria and 24 (8%) other Gram negative bacilli. Overall, blood culture was negative in 134/329 (41%) of cases of meningitis. At the time of reporting or discharge 25 babies had died [CFR 7.6, 95% CI: 5.0–11.0). Spn-specific CFR (19%) was significantly higher than GBS-Specific CRF (5%). An acute complication was identified in 78/304 (26%) of the survivors. Conclusion There remains a significant burden of bacterial meningitis in the first 3 months of life. The leading causes remain unchanged for the past three decades. Further work should be done on the prevention and early management of cases

Background Bacterial meningitis in infants We therefore set out to assess in detail the healthcare delivery of the management of bacterial meningitis among this age group in order to formulate better management strategies to improve outcome. Methods We conducted a detailed review of the medical records of infants with bacterial meningitis whose parents consented to take part in England and Wales between September 2010 and June 2013. Parents completed a questionnaire with details of the timing of onset and progression of features. All stages of care, including pre-hospital management, initial hospital assessment and ongoing care, post admission follow up were assessed. Ethics approval was by Cambridgeshire 2 REC (Ref: 10/H0308/64). Results During the study period 103 parents consented and 97 were confirmed cases. 66 (68%) were admitted from home and 31 (32%) were already in hospital prior to the onset of the meningitis. The median age was14 days (IQR 3–25) and was higher in home admissions 17 days (11–34) compared to cases already in hospital 1 day (0–7), p = 0.0001. Most 52 (54%) were males and 73 (76%) were born at term. Amongst cases admitted from home, 38% encountered inappropriate pre-hospital management. The median time (IQR) from onset of symptoms to first help was 4.8 h (2–10), triage to first dose of antibiotics was 1.7 h (1.0–3.3) and 54% received empiric antibiotics that were not as per NICE bacterial meningitis guideline. For cases in hospital already, the median time from onset to first dose of antibiotics was 2.6 h (1.3–k8.5) whilst 54% received empiric antibiotics that were not as per NICE bacterial meningitis guideline. Discussion The quality of clinical care for bacterial meningitis in infants