Implementing a toolkit for the prevention, management and control of carbapenemase-producing Enterobacteriaceae in English acute hospitals trusts:a qualitative evaluation

BACKGROUND: Antimicrobial resistance is an increasing problem in hospitals world-wide. Following other countries, English hospitals experienced outbreaks of carbapenemase-producing Enterobacteriaceae (CPE), a bacterial infection commonly resistant to last resort antibiotics. One way to improve CPE prevention, management and control is the production of guidelines, such as the CPE toolkit published by Public Health England in December 2013. The aim of this research was to investigate the implementation of the CPE toolkit and to identify barriers and facilitators to inform future policies. METHODS: Acute hospital trusts (N = 12) were purposively sampled based on their self-assessed CPE colonisation rates and time point of introducing local CPE action plans. Following maximum variation sampling, 44 interviews with hospital staff were conducted between April and August 2017 using a semi-structured topic guide based on the Capability, Opportunity, Motivation and Behaviour Model and the Theoretical Domains Framework, covering areas of influences on behaviour. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: The national CPE toolkit was widely disseminated within infection prevention and control teams (IPCT), but awareness was rare among other hospital staff. Local plans, developed by IPCTs referring to the CPE toolkit while considering local circumstances, were in place in all hospitals. Implementation barriers included: shortage of isolation facilities for CPE patients, time pressures, and competing demands. Facilitators were within hospital and across-hospital collaborations and knowledge sharing, availability of dedicated IPCTs, leadership support and prioritisation of CPE as an important concern. Participants using the CPE toolkit had mixed views, appreciating its readability and clarity about patient management, but voicing concerns about the lack of transparency on the level of evidence and the practicality of implementation. They recommended regular updates, additional clarifications, tailored information and implementation guidance. CONCLUSIONS: There were problems with the awareness and implementation of the CPE toolkit and frontline staff saw room for improvement, identifying implementation barriers and facilitators. An updated CPE toolkit version should provide comprehensive and instructive guidance on evidence-based CPE prevention, management and control procedures and their implementation in a modular format with sections tailored to hospitals' CPE status and to different staff groups

The first recorded outbreak of cryptosporidiosis due to Cryptosporidium cuniculus (formerly rabbit genotype), following a water quality incident

Background: We report the first identified outbreak of cryptosporidiosis with Cryptosporidium cuniculus following a water quality incident in Northamptonshire, UK. Methods: A standardised, enhanced Cryptosporidium exposure questionnaire was administered to all cases of cryptosporidiosis after the incident. Stool samples, water testing, microscopy slides and rabbit gut contents positive for Cryptosporidium were typed at the Cryptosporidium Reference Unit, Singleton Hospital, Swansea. Results: Twenty-three people were microbiologically linked to the incident although other evidence suggests an excess of 422 cases of cryptosporidiosis above baseline. Most were adult females; unusually for cryptosporidiosis there were no affected children identified under the age of 5 years. Water consumption was possibly higher than in national drinking water consumption patterns. Diarrhoea duration was negatively correlated to distance from the water treatment works where the contamination occurred. Oocyst counts were highest in water storage facilities. Conclusions: This outbreak is the first caused by C. cuniculus infection to have been noted and it has conclusively demonstrated that this species can be a human pathogen. Although symptomatically similar to cryptosporidiosis from C. parvum or C. hominis, this outbreak has revealed some differences, in particular no children under 5 were identified and females were over-represented. These dissimilarities are unexplained although we postulate possible explanations

Public health professionals' perceptions toward provision of health protection in England: a survey of expectations of Primary Care Trusts and Health Protection Units in the delivery of health protection

BACKGROUND: Effective health protection requires systematised responses with clear accountabilities. In England, Primary Care Trusts and the Health Protection Agency both have statutory responsibilities for health protection. A Memorandum of Understanding identifies responsibilities of both parties, but there is a potential lack of clarity about responsibility for specific health protection functions. We aimed to investigate professionals' perceptions of responsibility for different health protection functions, to inform future guidance for, and organisation of, health protection in England. METHODS: We sent a postal questionnaire to all health protection professionals in England from the following groups: (a) Directors of Public Health in Primary Care Trusts; (b) Directors of Health Protection Units within the Health Protection Agency; (c) Directors of Public Health in Strategic Health Authorities and; (d) Regional Directors of the Health Protection Agency RESULTS: The response rate exceeded 70%. Variations in perceptions of who should be, and who is, delivering health protection functions were observed within, and between, the professional groups (a)-(d). Concordance in views of which organisation should, and which does deliver was high (≥90%) for 6 of 18 health protection functions, but much lower (≤80%) for 6 other functions, including managing the implications of a case of meningitis out of hours, of landfill environmental contamination, vaccination in response to mumps outbreaks, nursing home infection control, monitoring sexually transmitted infections and immunisation training for primary care staff. The proportion of respondents reporting that they felt confident most or all of the time in the safe delivery of a health protection function was strongly correlated with the concordance (r = 0.65, P = 0.0038). CONCLUSION: Whilst we studied professionals' perceptions, rather than actual responses to incidents, our study suggests that there are important areas of health protection where consistent understanding of responsibility for delivery is lacking. There are opportunities to clarify the responsibility for health protection in England, perhaps learning from the approaches used for those health protection functions where we found consistent perceptions of accountability

Expansion of the 'Antibiotic Guardian' one health behavioural campaign across Europe to tackle antibiotic resistance: pilot phase and analysis of AMR knowledge

Antimicrobial resistance (AMR) is a major public health threat. The UK Antibiotic Guardian (AG) behavioural change campaign developed to tackle AMR was expanded across Europe through translation into Russian, Dutch and French. Demographics and knowledge of AGs were analyzed between 01 November 2016 and 31 December 2016. A total of 367 pledges were received with the majority from the public and health care professionals. The pilot has significantly increased the proportion of pledges from Europe (excluding UK) (chi2 = 108.7, P < 0.001). AMR knowledge was greater in AGs (including the public) compared to the EU Eurobarometer survey. Further promotion across Europe is required to measure an impact on tackling AMR

Whole genome sequencing in the investigation of recurrent invasive Group A streptococcus outbreaks in a maternity unit

Background: The clinical manifestations of Group A streptococcus (GAS) – (Streptococcus pyogenes) are diverse, ranging from asymptomatic colonisation to devastating invasive disease. Maternity related clusters of invasive Group A streptococcus (iGAS) infection are complex to investigate and control, especially if recurrent. Aim: We report on the investigation into three episodes of emm 75 GAS/iGAS infection in maternity patients at one hospital site over a 4 year period, two with monophyletic ancestry. Methods: The episodes are described, together with whole genome sequence isolate analyses. Single nucleotide polymorphism differences were compared with contemporaneous emm 75 genomes. Findings: Seven mothers had GAS/iGAS in over a 4 year period, emm 75, S.pyogenes and one had iGAS (in year 4) emm 3, S.pyogenes (subsequently discounted as linked). Three (clinical/screening samples) of the seven babies of emm 75 positive mothers and 3 screened healthcare workers were positive for GAS emm 75. Whole genome sequence similarity suggests a shared ancestral lineage and suggested a common source transmission but directionality of transmission cannot be inferred. However the findings indicate that persistence of a particular clone in a given setting may be long-term. Conclusions: Occupational health procedures were enhanced, staff were screened and antibiotic therapy provided to GAS positive staff and patients. The definitive source of infection could not be identified, although staff/patient transmission is the most likely route. The pattern of clonal GAS transmission over 4 years suggests long-term persistence of GAS may have occurred

National outbreak of Pseudomonas aeruginosa associated with an aftercare solution following piercings, July to September 2016, England.

We report a national Pseudomonas aeruginosa outbreak from a common source following piercings between July and September 2016 in England. The multi-agency outbreak investigation included active case finding, microbiological testing of environmental samples and case specimens including Variable Number Tandem Repeat (VNTR) typing and a retrospective cohort study. Overall, 162 outbreak cases (29 confirmed, 14 probable and 119 possible) and 14 non-outbreak cases were identified; all confirmed cases had ear piercings (93% cartilage). Outbreak cases were predominantly female (95%) and had a median age of 18 years (interquartile range: 13-56 years). Nineteen outbreak cases required surgery under general anaesthetic The same outbreak VNTR type (11,3,5,3,3,3,6,4,7) was isolated from bottles of an aftercare solution from a single manufacturer and in specimens from confirmed cases who attended eight different piercing studios supplied with this product. In the cohort study, use of aftercare solution was associated with becoming a case (aOR: 4.60, 95% confidence interval: 1.65-12.90). Environmental, microbiological and epidemiological investigations confirmed that contamination during production of aftercare solution was the source of this national outbreak; highlighting challenges in the regulation of a cosmetic products used in the piercing industry and that guidance on piercing aftercare may need to be reviewed

Electronic prescribing system design priorities for antimicrobial stewardship: a cross-sectional survey of 142 UK infection specialists.

The implementation of electronic prescribing and medication administration (EPMA) systems is a priority for hospitals and a potential component of antimicrobial stewardship (AMS).Accepted manuscript, 12 month embarg

p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8(+) T cells

T cell senescence is thought to contribute to immune function decline, but the pathways that mediate senescence in these cells are not clear. Here, we evaluated T cell populations from healthy volunteers and determined that human CD8+ effector memory T cells that reexpress the naive T cell marker CD45RA have many characteristics of cellular senescence, including decreased proliferation, defective mitochondrial function, and elevated levels of both ROS and p38 MAPK. Despite their apparent senescent state, we determined that these cells secreted high levels of both TNF-α and IFN-γ and showed potent cytotoxic activity. We found that the senescent CD45RA-expressing population engaged anaerobic glycolysis to generate energy for effector functions. Furthermore, inhibition of p38 MAPK signaling in senescent CD8+ T cells increased their proliferation, telomerase activity, mitochondrial biogenesis, and fitness; however, the extra energy required for these processes did not arise from increased glucose uptake or oxidative phosphorylation. Instead, p38 MAPK blockade in these senescent cells induced an increase in autophagy through enhanced interactions between p38 interacting protein (p38IP) and autophagy protein 9 (ATG9) in an mTOR-independent manner. Together, our findings describe fundamental metabolic requirements of senescent primary human CD8+ T cells and demonstrate that p38 MAPK blockade reverses senescence via an mTOR-independent pathway

A Methodological Framework for the Evaluation of Syndromic Surveillance Systems: A Case Study of England

Background: Syndromic surveillance complements traditional public health surveillance by collecting and analysing health indicators in near real time. The rationale of syndromic surveillance is that it may detect health threats faster than traditional surveillance systems permitting more timely, and hence potentially more effective public health action. The effectiveness of syndromic surveillance largely relies on the methods used to detect aberrations. Very few studies have evaluated the performance of syndromic surveillance systems and consequently little is known about the types of events that such systems can and cannot detect. Methods: We introduce a framework for the evaluation of syndromic surveillance systems that can be used in any setting based upon the use of simulated scenarios. For a range of scenarios this allows the time and probability of to be determined and uncertainty is fully incorporated. In addition, we demonstrate how such a framework can model the benefits of increases in the number of centres reporting syndromic data and also determine the minimum size of outbreaks that can or cannot be detected. Here, we demonstrate its utility using simulations of national influenza outbreaks and localised outbreaks of cryptosporidiosis. Results: Influenza outbreaks are consistently detected with larger outbreaks being detected in a more timely manner. Small cryptosporidiosis outbreaks (<1000 symptomatic individuals) are unlikely to be detected. We also demonstrate the advantages of having multiple syndromic data streams (e.g. emergency attendance data, telephone helpline data, general practice consultation data) as different streams are able to detect different types outbreaks with different efficacy (e.g. emergency attendance data are useful for the detection of pandemic influenza but not for outbreaks of cryptosporidiosis). We also highlight that for any one disease, the utility of data streams may vary geographically, and that the detection ability of syndromic surveillance varies seasonally (e.g. an influenza outbreak starting in July is detected sooner than one starting later in the year). We argue that our framework constitutes a useful tool for public health emergency preparedness in multiple settings. Conclusions: The proposed framework allows the exhaustive evaluation of any syndromic surveillance system and constitutes a useful tool for emergency preparedness and response