Antimicrobial resistance in China across human, animal, and environment sectors - a review of policy documents using a governance framework.

Antimicrobial resistance (AMR) poses a multifaceted threat to the human, animal, and environment sectors. In response, China has formulated a series of policies since the 2000s. Thus far, there has been no comprehensive assessment of these policy documents. This study aims to review the content of AMR policy documents at the national level using a governance framework covering three areas: Policy Design; Implementation Tools; and Monitoring and Evaluation. We identified 44 AMR documents from 2003 to 2022 sourced from government agency websites. Our findings have revealed noticeable discrepancies across the three governance areas. The Policy Design and Monitoring and Evaluation areas should be strengthened, particularly in the domains of 'Coordination', 'Accountability', 'Sustainability', and 'Effectiveness'. From a 'One Health' perspective, the environment sector has received less attention compared to the human and animal sectors. Effectively addressing these challenges requires a stronger commitment and widespread support from diverse stakeholders.

Clinical Uncertainty Influences Antibiotic Prescribing for Upper Respiratory Tract Infections: A Qualitative Study of Township Hospital Physicians and Village Doctors in Rural Shandong Province, China.

OBJECTIVE: This study aimed to explore how clinical uncertainty influences antibiotic prescribing practices among township hospital physicians and village doctors in rural Shandong Province, China. METHODS: Qualitative semi-structured interviews were conducted with 30 township hospital physicians and 6 village doctors from rural Shandong Province, China. A multi-stage random sampling method was used to identify respondents. Conceptual content analysis together with Colaizzi's method were used to generate qualitative codes and identify themes. RESULTS: Three final thematic categories emerged during the data analysis: (1) Incidence and treatment of Upper Respiratory Tract Infections (URTIs) in township hospitals and village clinics; (2) Antibiotic prescribing practices based on the clinical experience of clinicians; (3) Influence of clinical uncertainty on antibiotic prescribing. Respondents from both township hospitals and village clinics reported that URTIs were the most common reason for antibiotic prescriptions at their facilities and that clinical uncertainty appears to be an important driver for the overuse of antibiotics for URTIs. Clinical uncertainty was primarily due to: (1) Diagnostic uncertainty (establishing a relevant diagnosis is hindered by limited diagnostic resources and capacities, as well as limited willingness of patients to pay for investigations), and (2) Insufficient prognostic evidence. As a consequence of the clinical uncertainty caused by both diagnostic and prognostic uncertainty, respondents stated that antibiotics are frequently prescribed for URTIs to prevent both prolonged courses or recurrence of the disease, as well as clinical worsening, hospital admission, or complications. CONCLUSION: Our study suggests that clinical uncertainty is a key driver for the overuse and misuse of prescribing antibiotics for URTIs in both rural township hospitals and village clinics in Shandong province, China, and that interventions to reduce clinical uncertainty may help minimize the unnecessary use of antibiotics in these settings. Interventions that use clinical rules to identify patients at low risk of complications or hospitalization may be more feasible in the near-future than laboratory-based interventions aimed at reducing diagnostic uncertainty.

Towards a Better and Harmonized Education in Antimicrobial Stewardship in European Veterinary Curricula.

Education in antimicrobial stewardship (AMS) in veterinary medicine is essential to foster responsible antimicrobial use and control of antimicrobial resistance (AMR) in animals. AMS is listed by the EU and international organizations among the basic 'Day One Competences' required of veterinary students upon graduation. Our aim was to evaluate the quality of education of European veterinary students in AMS. We distributed a 27-item survey addressing the perceptions of preparedness and acquired skills on key topics related to AMS to final-year veterinary students in Europe. We collected 3423 complete answers from 89 veterinary schools in 30 countries. Selection of treatment strategies and awareness of emerging AMR problems were markedly different between countries. Overall, only one in four students was familiar with guidelines for antimicrobial use. The students perceived a medium-high impact of veterinary antimicrobial use on AMR in humans. Notably, 75% of the students felt the need for improved teaching on AMS, half of which also demanded more teaching on general antimicrobial therapy. Our results highlight several possible strategies to improve the quality of education, ranging from a better link between clinical rotations and the theory taught in pre-clinical modules, to a more effective introduction into best practices for antimicrobial use.

Variations in antibiotic prescribing among village doctors in a rural region of Shandong province, China: a cross-sectional analysis of prescriptions.

OBJECTIVES: To assess variation in antibiotic prescribing practices among village doctors in a rural region of Shandong province, China. DESIGN, SETTING AND PARTICIPANTS: Almost all outpatient encounters at village clinics result in a prescription being issued. Prescriptions were collected over a 2.5-year period from 8 primary care village clinics staffed by 24 doctors located around a town in rural Shandong province. A target of 60 prescriptions per clinic per month was sampled from an average total of around 300. Prescriptions were analysed at both aggregate and individual-prescriber levels, with a focus on diagnoses of likely viral acute upper respiratory tract infections (AURIs), defined as International Classification of Diseases, 10th Revision codes J00 and J06.9. MAIN OUTCOME MEASURES: Proportions of prescriptions for AURIs containing (1) at least one antibiotic, (2) multiple antibiotics, (3) at least one parenteral antibiotic; classes and agents of antibiotics prescribed. RESULTS: In total, 14 471 prescriptions from 23 prescribers were ultimately included, of which 5833 (40.3%) contained at least 1 antibiotic. Nearly two-thirds 62.5% (3237/5177) of likely viral AURI prescriptions contained an antibiotic, accounting for 55.5% (3237/5833) of all antibiotic-containing prescriptions. For AURIs, there was wide variation at the individual level in antibiotic prescribing rates (33.1%-88.0%), as well multiple antibiotic prescribing rates (1.3%-60.2%) and parenteral antibiotic prescribing rates (3.2%-62.1%). Each village doctor prescribed between 11 and 21 unique agents for AURIs, including many broad-spectrum antibiotics. Doctors in the highest quartile for antibiotic prescribing rates for AURI also had higher antibiotic prescribing rates than doctors in the lowest quartile for potentially bacterial upper respiratory tract infections (pharyngitis, tonsillitis, laryngopharyngitis; 89.1% vs 72.4%, p=0.002). CONCLUSIONS: All village doctors overused antibiotics for respiratory tract infections. Variations in individual prescriber practices are significant even in a small homogenous setting and should be accounted for when developing targets and interventions to improve antibiotic use.

Pattern of antibiotic prescribing and factors associated with it in eight village clinics in rural Shandong Province, China: a descriptive study.

BACKGROUND: This study describes the patterns of antibiotic prescribing in eight village clinics in rural China and evaluates factors associated with antibiotic prescribing using quantitative and qualitative methods. METHODS: From January 2015 to July 2017, 60 prescriptions were collected monthly from selected village clinics in Shandong, China. Village clinic doctors completed a questionnaire regarding their knowledge of antibiotic prescribing. Semi-structured interviews were conducted with 15 village doctors and 1 deputy director from the township hospital. RESULTS: Of the 14 526 prescriptions collected, 5851 (40.3%) contained at least one antibiotic, among which 18.4% had two or more antibiotics and 24.3% had parenteral antibiotics. The antibiotic prescribing rate (ß=-0.007 [95% confidence interval -0.009 to -0.004]) showed a declining trend (1.7% per month). Higher antibiotic prescribing rates were observed for patients <45 y of age and those diagnosed with upper respiratory tract infections and among village doctors who had less working experience and a lower level of knowledge on antibiotic prescribing. Qualitative analyses suggested that antibiotic prescribing was influenced by the patients' symptoms, patients' requests, policies restraining the overuse of antibiotics, subsidies for referral and routine village doctor training. CONCLUSIONS: Antibiotic prescribing has declined in the included village clinics, which may be due to the policy of reducing antibiotic overuse in primary health care centres in China.

Preparedness to prescribe antibiotics responsibly: a comparison between final year medical students in France and Sweden.

Students should graduate from medical school feeling prepared to prescribe antibiotics responsibly. We assessed self-reported preparedness among students at medical schools in Europe, and we focus here on the results from students in Sweden and France, countries with wide differences in the intensity of antibiotic consumption and burden of antibiotic resistance. We conducted a cross-sectional web-based survey in 2015, based on a comprehensive set of topics related to prudent antibiotic use. All final year students at a medical school in France or Sweden were eligible to participate. Preparedness scores were calculated for each student, and mean scores were compared at medical school and country levels. Comparisons were also made on availability of teaching methods. We received responses from 2085/7653 (response rate 27.2%) students from 31/34 eligible medical schools in France and 302/1124 (26.9%) students from 7/7 schools in Sweden. The relative ranking order of curriculum topics by preparedness level was consistent between countries, but students in Sweden had higher self-reported levels of preparedness in 21/27 topics. There was higher availability for eight of nine teaching methods at Swedish medical schools. Students in France were more likely to report a need for further education on antibiotic use (63.5% vs. 20.3%, p < 0.001). Final year students in France report lower levels of preparedness, less availability of teaching methods and higher needs for more education on antibiotic use. Furthermore, we have identified specific areas for improvement in education on prudent antibiotic use in both Sweden and France.

Presence of antibiotic residues in various environmental compartments of Shandong province in eastern China: Its potential for resistance development and ecological and human risk.

OBJECTIVES: To investigate the occurrence of antibiotic residues in different types of environmental samples including water samples in rural Shandong province, China. Further, to characterize the potential ecological risk for development of antibiotic resistance in the environment, and the potential direct human health risk of exposure to antibiotics via drinking water and vegetables. METHODS: Environmental samples (n = 214) (river water, waste water, drinking water, sediments, manure, soil and edible parts of vegetables) were collected in twelve villages in Shandong province in eastern China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to determine the concentration of antibiotic residues. The ratio of the measured environmental concentrations (MEC) to the predicted no-effect concentrations (PNEC) was used to evaluate the ecological risk (risk quotient, RQ) for development of antibiotic resistance. The potential risks to human health through exposure to antibiotics in drinking water were assessed by comparing measured environmental concentrations (MEC) and predicted no-effect concentration in drinking water (PNECDW), and in vegetables by comparing estimated daily intake (EDI) to ADI. RESULTS: Sulfapyridine, sulfamethoxazole, ciprofloxacin, enrofloxacin, levofloxacin, norfloxacin, chloramphenicol, florfenicol, doxycycline, and metronidazole were detected at concentrations ranging between 0.3 and 3.9 ng/L in river water, 1.3 and 12.5 ng/L in waste water, 0.5 and 21.4 ng/L in drinking water, 0.31 and 1.21 µg/kg in river sediment, 0.82 and 1.91 µg/kg in pig manure, 0.1 and 11.68 µg/kg in outlet sediment, 0.5 and 2.5 µg/kg in soil, and 6.3 and 27.2 µg/kg in vegetables. The RQs for resistance development were >1 for enrofloxacin, levofloxacin, and ranged between 0.1 and 1 for ciprofloxacin. MECs/PNECDW ratios were <1 from exposure to antibiotics through drinking water for both adults and children. EDI/ADI ratios were <0.1 from exposure to antibiotics by vegetable consumption. CONCLUSIONS: Antibiotic pollutants were ubiquitous in various environmental compartments of Shandong province of China. Risk estimates indicated a potential for the measured levels of enrofloxacin, levofloxacin and ciprofloxacin in waste water to pose an ecological risk for resistance selection, and further studies are needed to validate this finding. The investigated antibiotics did not appear to pose an appreciable direct human health risk from environmental exposure through drinking water or vegetables consumption. However, they might still pose a risk for resistance development.

Assessing the Knowledge, Attitudes and Behaviors of Human and Animal Health Students towards Antibiotic Use and Resistance: A Pilot Cross-Sectional Study in the UK.

The Global Action Plan on Antimicrobial Resistance highlights the importance of training all healthcare professionals. No study has assessed patterns of students' knowledge, attitudes and practices concerning antibiotic use simultaneously across different healthcare course types. We conducted a cross-sectional multi-center survey among UK students. The survey was advertised through local survey coordinators at 25 universities. The online survey was accessible from 10th October to 17th November 2016 (before European Antibiotic Awareness Day). A total of 255 students from 25 universities participated, including students on medicine, pharmacy, nursing, physician associate, dentistry and veterinary medicine courses. Antibiotic resistance was considered to be a more important global challenge than climate change, obesity or food security (p < 0.001). Most students (95%) believed that antibiotic resistance will be a problem for their future practice, but fewer (69%) thought that the antibiotics they will prescribe, administer or dispense will contribute to the problem. A fifth of students felt they had sufficient knowledge of antibiotic use for their future work. Our exploratory study suggests that UK human and animal healthcare students are aware of the importance of antibiotic resistance, but many still have certain misconceptions. Campaigns and improved educational efforts applying behavioral insights methodology could address these.

Study protocol for One Health data collections, analyses and intervention of the Sino-Swedish integrated multisectoral partnership for antibiotic resistance containment (IMPACT).

INTRODUCTION: To effectively minimise the emergence and dissemination of antibiotic resistant bacteria, a holistic One Health approach is called for. The Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance Containment is a cross-sectoral and integrated project on antibiotic resistance, conducted in Shandong Province in China. This paper outlines the overall study protocol for the project. To our knowledge, this is the first research programme aiming to take a true holistic approach across multiple sectors simultaneously in China, and the first to incorporate both antibiotic use and infection prevention and control in addition to antibiotic resistance patterns. The project aims to address gaps in current knowledge and seeks to improve the situation through a system-wide intervention. By using a One Health approach we can address important research questions that individual discipline investigations are unable to. The results obtained should thus more closely reflect the world in which human health, animal health and the environment are inextricably and intimately interlinked. METHODS AND ANALYSIS: Both quantitative and qualitative studies are included for households from 12 villages, their surrounding environment and a tertiary care hospital in a nearby town. The studies include analyses of antibiotic consumption for humans and pigs; qualitative and quantitative data on perceptions, knowledge and attitudes; faecal carriage of extended spectrum ß-lactamase and carbapenemase-producing Enterobacteriaceae from pigs and humans, and occurrence in household drinking water, surface water, waste water and clinical bacterial isolates from the hospital. Carriage of methicillin-resistant Staphylococcus aureus in humans, household pigs and clinical bacterial isolates is also investigated. Furthermore, potential inter-relationships between these sources are analysed. A multifaceted One Health intervention is designed and implemented in 6 of the 12 villages. Repeated and continuous data collections take place over 2 years, where the repeated data collection is performed after 1 year of intervention. Comparisons are made between intervention and control villages, before and after the intervention. ETHICS: Ethics approval was obtained from the first Affiliated Hospital, College of Medicine, Zhejiang University, China, reference number 2015#185 and 2015#283.

Using antibiotics responsibly: are we there yet?

Problems of antibiotic access and excess coexist in the world today and are compounded by rising rates of antibiotic resistance. We introduce two dimensions of responsibility to this context: responsible individual practices and a broad societal obligation centered on sustainability. Acting on these responsibilities requires recognizing the potential tensions between an individual optimum for antibiotic use and the societal optimum. We relate the tragedy of the commons metaphor to this situation to illustrate the complexity involved, and we draw on real-world experiences in Uganda, India, China and France. We conclude that we must form a global stewardship of antibiotics that can link access, innovation and conservation efforts across countries to ensure sustainable access to effective antibiotics for all who need them.

Trends and patterns of antibiotic consumption in Shanghai municipality, China: a 6 year surveillance with sales records, 2009-14.

OBJECTIVES: The objective of this study was to identify the trends and patterns of total antibiotic use in Shanghai from 2009 to 2014. METHODS: Sales records were collected from a minimum of 160 hospitals and 241 primary healthcare settings and used as a proxy for consumption. Antibiotic sales expressed in DDD per 1000 inhabitants per day (DID) were calculated. We compared patterns of antibiotic use in the Shanghai municipality, populated by 24 million inhabitants, with European countries using indicators from the European Surveillance of Antimicrobial Consumption (ESAC). RESULTS: Total antibiotic use was highest at 25.9 DID in 2010, fell to 17.8 DID in 2012 and remained stable thereafter. The majority of this reduction occurred over 6 months in 2011. In 2014, two-thirds of the antibiotic sales were to hospitals (serving both inpatients and outpatients) and one-third to primary healthcare institutions. Cephalosporins accounted for 50.2% of total DID, followed by macrolides (18.2%), quinolones (16.0%) and penicillins (7.3%). A fifth of all antibiotics were used in parenteral form. CONCLUSIONS: We have successfully used aggregated sales data to monitor antibiotic usage across a large urban population over a 6 year period. A rapid, substantial and sustained reduction in antibiotic usage across the entire health system occurred. This coincided with several interventions across hierarchies in the health sector, including a national campaign. The patterns of antibiotic use indicate persistent preferences for cephalosporins, macrolides, quinolones and parenteral preparations. Further efforts are needed to investigate and improve the quality of antibiotic use.

Building bridges to operationalise one health - A Sino-Swedish collaboration to tackle antibiotic resistance.

Antibiotic resistance is a complex global health challenge. The recent Global Action Plan on antimicrobial resistance highlights the importance of adopting One Health approaches that can cross traditional disciplinary boundaries. We report on the early experiences of a multisectoral Sino-Swedish research project that aims to address gaps in our current knowledge and seeks to improve the situation through system-wide interventions. Our research project is investigating antibiotic use and resistance in a rural area of China through a combination of epidemiological, health systems and laboratory investigations. We reflect here on the challenges inherent in conducting long distance cross-disciplinary collaborations, having now completed data and sample collection for a baseline situation analysis. In particular, we recognise the importance of investing in aspects such as effective communication, shared conceptual frameworks and leadership. We suggest that our experiences will be instructive to others planning to develop similar international One Health collaborations.

High prevalence of antibiotic resistance in commensal Escherichia coli among children in rural Vietnam.

BACKGROUND: Commensal bacteria represent an important reservoir of antibiotic resistance genes. Few community-based studies of antibiotic resistance in commensal bacteria have been conducted in Southeast Asia. We investigated the prevalence of resistance in commensal Escherichia coli in preschool children in rural Vietnam, and factors associated with carriage of resistant bacteria. METHODS: We tested isolates of E. coli from faecal samples of 818 children aged 6-60 months living in FilaBavi, a demographic surveillance site near Hanoi. Daily antibiotic use data was collected for participating children for three weeks prior to sampling and analysed with socioeconomic and demographic characteristics extracted from FilaBavi's re-census survey 2007. Descriptive statistics were generated, and a logistic regression model was used to identify contributions of the examined factors. RESULTS: High prevalences of resistance were found to tetracycline (74%), co-trimoxazole (68%), ampicillin (65%), chloramphenicol (40%), and nalidixic acid (27%). Two isolates were resistant to ciprofloxacin. Sixty percent of isolates were resistant to three or more antibiotics. Recent sulphonamide use was associated with co-trimoxazole resistance [OR 3.2, 95% CI 1.8-5.7], and beta-lactam use with ampicillin resistance [OR 1.8, 95% CI 1.3-2.4]. Isolates from children aged 6-23 months were more likely to be resistant to ampicillin [OR 1.8, 95% CI 1.3-2.4] and co-trimoxazole [OR 1.5, 95% CI 1.1-2.0]. Associations were identified between geographical areas and tetracycline and ampicillin resistance. CONCLUSIONS: We present high prevalence of carriage of commensal E. coli resistant to commonly used antibiotics. The identified associations with recent antibiotic use, age, and geographical location might contribute to our understanding of carriage of antibiotic resistant commensal bacteria.

Detection of polyomavirus BK reactivation after renal transplantation using an intensive decoy cell surveillance program is cost-effective.

BACKGROUND: Reactivation of polyomavirus BK (BKV) after renal transplantation can lead to allograft dysfunction or loss with early detection improving outcomes. Current guidelines recommend quantitative polymerase chain reaction for surveillance; however, urinary decoy cell detection is a potentially cost-effective alternative. We present the outcomes from an early intensive BKV surveillance program using decoy cell detection for initial screening starting 2 weeks after transplantation. METHODS: Records for all recipients of kidney (n=211) or simultaneous kidney and pancreas (n=102) transplants performed over 2 years in a single center were reviewed. Follow-up was for a minimum of 1 year. Urine cytology screening was performed fortnightly from 0 to 3 months after transplantation, monthly from 3 to 6 months then every 2 months from 6 to 12 months. RESULTS: Decoy cell positivity occurred in 56 of 313 patients (17.9%) with sustained decoy cell positivity (≥2 positive urine samples >2 weeks apart) present in 32 patients (10.2%). Twenty-four patients (7.6%) became viremic and three patients (1%) developed polyoma virus nephropathy. The median time after transplantation until decoy cell positivity was 78 days, decreasing to 67 days for patients with sustained positivity and 57 days for patients who developed polyoma virus nephropathy. No grafts were lost due to BKV during the study period. Decoy cell screening resulted in savings of approximately £135,000 over 2 years, when compared with routine surveillance by quantitative polymerase chain reaction. CONCLUSIONS: Clinically significant BKV reactivation occurs early after transplantation and can be reliably detected by decoy cell screening. A surveillance strategy for detecting BKV reactivation based on urine cytology is cost-effective.