Pathways to optimising antibiotic use in Anhui: Identifying key determinants in community and clinical settings

Widespread antibiotic use is considered to be a major contributor to the growing problem of antimicrobial resistance in many countries, but there is a lack of evidence regarding its key drivers in China, particularly in rural settings and outside hospitals, and whether these differ from those found elsewhere. This evidence is essential for identifying the health system, behavioural and policy interventions that have most potential for limiting the spread of antibiotic resistance in China, while ensuring equitable access to antibiotics for essential treatment of bacterial infections. This innovative interdisciplinary project aims to acquire greater understanding of key social, economic, cultural, systemic and other influences on antibiotic use by investigating and quantifying current use of both prescribed and non-prescribed antibiotics and other forms of care to treat common infections in rural parts of Anhui Province. Our study will document treatment-seeking practices for selected common infections from all sources (including informal, Traditional Chinese Medicine (TCM), folk, home-based, private and government medical care) among patients at local health facilities and in the general population. We will gather information on testing, clinical diagnosis and antibiotic treatment procedures at lower levels of the health system and on over-the-counter purchasing of antibiotics from pharmacies and medicine shops. We will ascertain the annual incidence of common respiratory tract infections in the population of Anhui Province and assess the effects of the different forms of treatment they use, including antibiotics, on reported severity and duration of illness. We will also ascertain the feasibility of assessing clinical diagnostic accuracy, relationship between patient-reported symptoms and clinical diagnosis, and burden of antibiotic resistance in non-hospitalised patients, and investigate possible population biases in existing laboratory data through microbiological sampling. This range of evidence will enable us to formulate recommendations for appropriate interventions to optimise the use of antibiotics in Anhui Province and other regions of China.

1.1: Microbiological sampling (Objectives 2, 4, 5, 10): 1,000 patients will be recruited for the COPD study in order to collect 100 S.pneumoniae, and 278 (555) patients in order to collect 100 (200) E.coli for the cUTI study, based on these assumptions: 40% of patients recruited to cUTI study and 25% of patients recruited to COPD will yield a pathogen; 90% of pathogens isolated from urine will be E.coli and 40% of pathogens isolated from sputum will be S.pneumoniae. In E.coli, resistance to nitrofurantoin, fosfomycin and co-amoxiclav will be <5%, resistance to cephalosporins and fluoroquinolones 50-60% (Qiao L-D, Chen S, Yang Y et al, 2013); in S.pneumoniae, penicillin resistance will be 12.5% and erythromycin 90% (Kim S-H, Song J-H, Chung D-R et al, 2012)
2.4: Direct Observations at pharmacies (Objectives 2, 6, 11): An observer is at each site for two 7-day periods, each spaced over 4 consecutive seasons (92 person-days of observations over 16 periods in 2x2x4 settings). All encounters in observation days are eligible for observation, using a structured checklist.
3.1 Prospective population cohort survey (Objectives 1, 2, 8, 9): Cases will be households, selected through cluster-randomization with 3 steps: (1) divides all counties in the Province into north, middle & south regions; (2) randomly selects 6 counties from each region, then 1 township and community from each county & 1 administrative village & 1 street from each selected township or community; (3) randomly draws 1 household from each administrative village (or street) as a starting point, then every 5th household using a random walk method. Baseline survey uses a structured questionnaire. A local informant completes case detection in cohort households bi-weekly for 12 months using a symptom checklist. Cases are reported by text message for follow-up in person or by phone using structured questionnaires. Data analysis will use descriptive statistics & multivariate modelling.

Beneficiaries of the research
This research will benefit Chinese patients, clinicians and policy makers looking to optimise antimicrobial stewardship and reduce antibiotic resistance (ABR) in China. The identification of the current drivers of antibiotic prescribing in Anhui Province will be relevant to health services delivered in both hospital and community health care settings and both urban and rural areas. Resulting policy change recommendations will inform behaviour and service changes which will reduce antibiotic prescribing and AMR in Anhui and are likely to be transferable to other areas of China.
The optimisation of antibiotic prescribing and reductions in ABR will benefit the welfare of the residents of Anhui and (depending on implementation) of China. This research will support health care providers and policy makers to make decisions based on up to date China-specific evidence. It will identify key behaviours and systems which could be targeted with interventions and potential facilitators and barriers to change. Optimisation of antibiotic prescribing will contribute to more efficient use of health care resources and ultimately to reduced morbidity and mortality from resistant infections.
This collaborative project will strengthen the research links between UK and China, promote the exchange of expertise and produce internationally excellent research. The UK team will contribute their expertise in research methods (especially large anthropological studies, observational studies and behaviour change intervention design) and support the China team through training and joint research activities. This will enable the team at Anhui University to develop their ABR research programme, which will benefit researchers and research users in China in the long term.
Engagement activities
Throughout the research project we will engage with key government and non-governmental bodies involved in managing antibiotic use, antimicrobial stewardship and reduction of ABR. The Anhui Provincial Commission of Health and Family Planning is supporting the research and will identify other relevant stakeholders to join our advisory group. This group will meet at the start of the project to advise on key contextual issues, receive regular updates on progress, review and comment on finding and collaborate on developing a plan for implementing recommendations. In this way we will ensure that the research is relevant to the needs of local and national actors in ABR reduction and that important stakeholders are involved from the beginning.
Research findings will be disseminated through a range of academic and public engagement activities, published in peer-reviewed internationally recognised journals and presented at academic conferences in China, the UK and other relevant scientific meetings internationally. Key findings and recommendations will be presented to the main stakeholders in ABR reduction in Anhui, including health authorities, clinicians, pharmacists, pharmaceutical suppliers and other health professionals. We will produce tailored policy recommendations to fit with existing policies such as the Special Antimicrobial Use Rectification program.
Plan for Impact
Results of the proposed research will be summarised and disseminated to relevant stakeholders in developing antibiotic stewardship policies. We will provide research summaries to health service managers and policy makers. At the end of the project we will host an "implementation meeting" to which all relevant stakeholders will be invited and at which we will present (and disseminate) summaries of the research and where we will (in partnership with stakeholders) establish how our results are best implemented. We anticipate the proposed research will inform the design of future antimicrobial stewardship interventions, as well as the research to evaluate these interventions, for which we plan to seek further (separate) funding.