Comparison of China's and the European Union's Approaches to Antimicrobial Stewardship in the Pork Industry.

Antimicrobial resistance (AMR) is a recognized global public health concern. Although the link between antimicrobial usage in food animals and AMR in humans is established, the detailed interactions are unclear. Antimicrobial stewardship (AMS) in livestock was first implemented in Europe with Sweden as the pioneer in 1986. Despite this head start, AMR is still an ongoing challenge for Europe. The European Union (EU) is an established agriculture producer, the second largest pork producer globally, and one of the largest markets for organic food. China is the global leader in both production and consumption of pork. China's rise in prosperity has led to an increase in its pork demand. Chinese producers commonly use antimicrobials during production for disease treatment and prevention to meet this increased demand. China's rising prosperity together with recent publicized food safety scandals, disease outbreaks in domestic livestock products, and increased AMR awareness have resulted in an increased willingness to pay and demand for organic food by Chinese consumers. Responding to the growing concerns of AMR by consumers and the World Health Organization (WHO), the Chinese government introduced a national pilot program in 2016 to reduce unnecessary antimicrobial use. Compared with China, the EU is a different entity as it is a political union comprising diverse countries and although it may have more experience in AMS, both entities face similar issues with AMR and increasing demand for organic food. Increased interest in organic food has arisen due to concerns about AMR, food safety, outbreaks of bacterial food contamination, and animal welfare. This article aims to compare the different AMS strategies employed by each entity, China and the EU, and how the increased demand for organic produce globally also influences the effort to reduce antimicrobial use in these entities' pork industries.

An efficient cephalosporin stewardship programme in French swine production.

By 2010, systems set up to monitor the antimicrobial resistance of pathogenic bacteria and antimicrobial usage identified a sustained increase regarding third- and fourth-generation cephalosporin resistance in French pig production. This sector mobilised and collectively committed to responsible action in the following months. This led to a multi-professional voluntary stewardship programme that was started in 2011. A consensus of veterinary opinion led to the definition of restrictive rules on the prescription of the third- and fourth-generation cephalosporins targeted by the antimicrobial stewardship programme (ASP). All pig sector professionals, including farmers, were informed. Existing monitoring systems for usage and resistance were supplemented by data from the records of veterinarians' cephalosporin deliveries and from individual pig farm surveys investigating antimicrobial usage. The second step, from 2014, entailed regulatory measures that consolidated the programme by setting quantitative reduction objectives and specifying the terms and conditions for prescribing and dispensing a list of critical antimicrobial molecules including cephalosporins. All the data sources confirmed a significant fall of more than 90% in cephalosporin usage in the French pig production sector between 2010 and 2016. Monitoring systems recorded that the resistance of commensal and pathogenic Escherichia coli isolates also tended to decrease over the same period. The stewardship programme proved highly effective in reducing usage and containing resistance, illustrating the efficiency of a well-defined multi-professional strategy.

Poor compliance with an antibiotic directive-A call for intensified monitoring.

BACKGROUND: In April 2017, the Central Denmark Region Antibiotic Stewardship Committee issued a directive to reduce the general use of piperacillin-tazobactam and prescribe narrow-spectrum antibiotics for mild and moderate pneumonia. The directive was distributed to all regional hospital clinicians. METHODS: Electronic medical records were used to obtain de-identified details of all antibiotics administered (together with diagnosis codes) to all in-hospital patients (pre-directive and post-directive) in the nine regional hospitals. Average moving range statistical process control charts were used to analyze pre-directive and post-directive variation in antibiotic usage patterns. RESULTS: Upon the distribution of the directive, a period of decline of the overall usage of piperacillin-tazobactam ensued. Rather than benzylpenicillin, as recommended for pneumonia, the initial decline in piperacillin/tazobactam usage was accompanied by increased use of cefuroxime. CONCLUSIONS: A steward-directed reduction in piperacillin-tazobactam usage was accompanied by less desirable usage of a broad-spectrum alternative. Future antibiotic stewardship initiatives will hopefully benefit from close monitoring and timely feedback to clinicians. A dialogue with clinicians based on near real-time data is predicted to improve antibiotic stewardship actions.

Antimicrobial multidrug resistance in the era of COVID-19: a forgotten plight?

BACKGROUND: Antimicrobial resistance (AMR) is a growing global problem to which the ongoing COVID-19 pandemic may further contribute. With resources deployed away from antimicrobial stewardship, evidence of substantial pre-emptive antibiotic use in COVID-19 patients and indirectly, with deteriorating economic conditions fuelling poverty potentially impacting on levels of resistance, AMR threat remains significant. MAIN BODY: In this paper, main AMR countermeasures are revisited and priorities to tackle the issue are re-iterated. The need for collaboration is stressed, acknowledging the relationship between human health, animal health and environment ("One Health" approach). Among the stated priorities, the initiative by the European Medicines Regulatory Network to further strengthen the measures in combatting AMR is highlighted. Likewise, it is asserted that other emerging health threats require global collaboration with the One Health approach offering a valuable blueprint for action. CONCLUSION: The authors stress the importance of an integrated preparedness strategy to tackle this public health peril.

Legal implications of antibiotic stewardship programs.

Infectious diseases professional societies, public health agencies, and healthcare regulatory agencies call for antibiotic stewardship programs (ASP) in many healthcare settings. However, medical legal implications of these programs remain largely uncharted territory. Although there is no legal precedent addressing issues of liability and standards of care on this subject, anticipating how the courts may assess questions of medical liability with respect to the various components of ASPs is important to define best practices in ASP operations, not only to manage the potential risk but also to improve patient care. This article seeks to address some of the common processes and interventions involved in antibiotic stewardship and the potential professional liability implications of these activities.

Antimicrobial resistance associations with national primary care antibiotic stewardship policy: Primary care-based, multilevel analytic study.

BACKGROUND: Recent UK antibiotic stewardship policies have resulted in significant changes in primary care dispensing, but whether this has impacted antimicrobial resistance is unknown. AIM: To evaluate associations between changes in primary care dispensing and antimicrobial resistance in community-acquired urinary Escherichia coli infections. METHODS: Multilevel logistic regression modelling investigating relationships between primary care practice level antibiotic dispensing for approximately 1.5 million patients in South West England and resistance in 152,704 community-acquired urinary E. coli between 2013 and 2016. Relationships presented for within and subsequent quarter drug-bug pairs, adjusted for patient age, deprivation, and rurality. RESULTS: In line with national trends, overall antibiotic dispensing per 1000 registered patients fell 11%. Amoxicillin fell 14%, cefalexin 20%, ciprofloxacin 24%, co-amoxiclav 49% and trimethoprim 8%. Nitrofurantoin increased 7%. Antibiotic reductions were associated with reduced within quarter same-antibiotic resistance to: amoxicillin, ciprofloxacin and trimethoprim. Subsequent quarter reduced resistance was observed for trimethoprim and amoxicillin. Antibiotic dispensing reductions were associated with increased within and subsequent quarter resistance to cefalexin and co-amoxiclav. Increased nitrofurantoin dispensing was associated with reduced within and subsequent quarter trimethoprim resistance without affecting nitrofurantoin resistance. CONCLUSIONS: This evaluation of a national primary care stewardship policy on antimicrobial resistance in the community suggests both hoped-for benefits and unexpected harms. Some increase in resistance to cefalexin and co-amoxiclav could result from residual confounding. Randomised controlled trials are urgently required to investigate causality.

Veterinary antimicrobial resistance containment in Bangladesh: Evaluating the national action plan and scoping the evidence on implementation.

OBJECTIVES: In 2015, the World Health Organization (WHO) released its global action plan (GAP) on antimicrobial resistance (AMR) as a blueprint for the design of national action plans for AMR containment. Bangladesh, with 80% rural household ownership of at least one livestock, introduced its national action plan in May 2017. The objective of this study was two-fold: (i) to perform a policy content evaluation of the Bangladesh National Action Plan (BNAP) against the GAP with a focus on veterinary AMR containment strategies; and (ii) to assess the evidence on the implementation of veterinary AMR containment strategies of the BNAP. METHODS: The BNAP was evaluated against the GAP to identify commonalities and policy gaps. A scoping review of peer-reviewed and grey literature was performed to identity evidence of policy implementation and practice gaps. RESULTS: The BNAP is strongly aligned with the GAP. However, the study identified policy gaps, including an explicit financing modality, specifications for antimicrobial stewardship (AMS) in the veterinary sector, and rigorous operational and monitoring & evaluation frameworks. More evidence on implementation is needed in terms of incorporation of AMR in the curriculum of veterinarians, AMS plans throughout the veterinary sector, and infection prevention and control protocols and implementation. CONCLUSION: Closing the identified gaps is essential for successful veterinary AMR containment in Bangladesh but will require sustained and significant investment in institutional and human resource development in the coming years.

Nonprescription sale of schedule H1 antibiotics in a city of South India.

CONTEXT: The acquisition of antibiotic without a prescription by the general population is a typical practice found in community pharmacies across India, which is a notable contributor of antimicrobial resistance. According to the present regulation in India, sale of certain antimicrobials included in schedule H1 without prescription is unlawful. In this contest, a program was organized by the Drug Control Administration, Government of Andhra Pradesh, to educate pharmacists regarding schedule H1. AIMS: The aim of our study is to assess the impact of the program on the rate of antibiotics dispensed at community pharmacies. SETTINGS AND DESIGN: A cross-sectional study was designed to investigate the nonprescription sale of antibiotics, from September to December 2018 through 200 community pharmacies located in and around Guntur city located in the state of Andhra Pradesh in India. SUBJECTS AND METHODS: A simulated client methodology was used in this study. A total of 3 female actors including an author of this present study are prior trained to present a standardized simulation of clinical conditions (sore throat, urinary tract infection, cold, and fever) to the pharmacist at the community pharmacies. STATISTICAL ANALYSIS USED: Microsoft excel sheet was used for data analysis. RESULTS: The simulated patients successfully obtained antibiotic from 78% pharmacies with the highest rate of urinary tract infection when compared to other conditions. Pharmacists who objected to dispense antibiotics (22%) are found in developed locations in the city and appeared well qualified. CONCLUSIONS: The present study revealed that the antibiotics are continued to be sold without prescription even after the education program on schedule H1. The deregulation of the act is definitely the problem to be addressed by the government.

Impact of national interventions to promote responsible antibiotic use: a systematic review.

BACKGROUND: Global recognition of antimicrobial resistance (AMR) as an urgent public health problem has galvanized national and international efforts. Chief among these are interventions to curb the overuse and misuse of antibiotics. However, the impact of these initiatives is not fully understood, making it difficult to assess the expected effectiveness and sustainability of further policy interventions. We conducted a systematic review to summarize existing evidence for the impact of nationally enforced interventions to reduce inappropriate antibiotic use in humans. METHODS: We searched seven databases and examined reference lists of retrieved articles. To be included, articles had to evaluate the impact of national responsible use initiatives. We excluded studies that only described policy implementations. RESULTS: We identified 34 articles detailing interventions in 21 high- and upper-middle-income countries. Interventions addressing inappropriate antibiotic access included antibiotic committees, clinical guidelines and prescribing restrictions. There was consistent evidence that these were effective at reducing antibiotic consumption and prescription. Interventions targeting inappropriate antibiotic demand consisted of education campaigns for healthcare professionals and the general public. Evidence for this was mixed, with several studies showing no impact on overall antibiotic consumption. CONCLUSIONS: National-level interventions to reduce inappropriate access to antibiotics can be effective. However, evidence is limited to high- and upper-middle-income countries, and more evidence is needed on the long-term sustained impact of interventions. There should also be a simultaneous push towards standardized outcome measures to enable comparisons of interventions in different settings.

Antimicrobial use policy change in pre-weaned dairy calves and its impact on antimicrobial resistance in commensal Escherichia coli: a cross sectional and ecological study.

BACKGROUND: This study is based on data collected to investigate the relation of peri-parturient events (colostrum quality, passive transfer of immunity, calving difficulty) on calf health and antimicrobial use. A component of the study was to provide feedback to farm management to identify calves at risk for disease and promote antimicrobial stewardship. At the start of the study (May 2016), a combination of enrofloxacin, penicillin, and sulfamethoxazole was the first treatment given to clinically abnormal calves. Based on feedback and interaction between study investigators, farm management and consulting veterinarians, a new policy was implemented to reduce antimicrobial use in calves. In August, the first treatment was changed to a combination of ampicillin and sulfamethoxazole. In September, the first treatment was reduced to only sulfamethoxazole. We investigated the effects of these policy changes in antimicrobial use on resistance in commensal Escherichia coli. RESULTS: We enrolled 4301 calves at birth and documented antimicrobial use until weaning. Most calves (99.4%) received antimicrobials and 70.4% received a total of 2-4 treatments. Antimicrobial use was more intense in younger calves (≤ 28 days) relative to older calves. We isolated 544 E. coli from fecal samples obtained from 132 calves. We determined resistance to 12 antimicrobials and 85% of the isolates were resistant to at least 3 antimicrobial classes. We performed latent class analysis to identify underlying unique classes where isolates shared resistance patterns and selected a solution with 4 classes. The least resistant class had isolates that were mainly resistant to only tetracycline and sulfisoxazole. The other 3 classes comprised isolates with resistance to ampicillin, chloramphenicol, aminoglycosides, sulfonamides, tetracycline, in addition to either ceftiofur; or nalidixic acid; or ciprofloxacin plus nalidixic acid and ceftiofur. Overall, E coli from younger calves and calves that received multiple treatments were more likely to have extensive resistance including resistance to fluoroquinolones and ceftiofur. In general, there was a declining trend in resistance to most antimicrobials during and after policy changes were implemented, except for ampicillin, ciprofloxacin, ceftiofur and gentamicin. CONCLUSIONS: Information feedback to farms can influence farm managers to reduce antimicrobial use and this can change endemic farm resistance patterns.

The glocalization of antimicrobial stewardship.

This brief commentary argues that glocal governance introduces a fruitful new perspective to the global governance debate of AMR, and cautions against too strict a focus on establishing globally binding governance regimes for curbing AMR.

Adaptation of the WHO Essential Medicines List for national antibiotic stewardship policy in England: being AWaRe.

OBJECTIVES: Appropriate use of and access to antimicrobials are key priorities of global strategies to combat antimicrobial resistance (AMR). The WHO recently classified key antibiotics into three categories (AWaRe) to improve access (Access), monitor important antibiotics (Watch) and preserve effectiveness of 'last resort' antibiotics (Reserve). This classification was assessed for antibiotic stewardship and quality improvement in English hospitals. METHODS: Using an expert elicitation exercise, antibiotics used in England but not included in the WHO AWaRe index were added to an appropriate category following a workshop consensus exercise with national experts. The methodology was tested using national antibiotic prescribing data and presented by primary and secondary care. RESULTS: In 2016, 46/108 antibiotics included within the WHO AWaRe index were routinely used in England and an additional 25 antibiotics also commonly used in England were not included in the WHO AWaRe index. WHO AWaRe-excluded and -included antibiotics were reviewed and reclassified according to the England-adapted AWaRE index with the justification by experts for each addition or alteration. Applying the England-adapted AWaRe index, Access antibiotics accounted for the majority (60.9%) of prescribing, followed by Watch (37.9%) and Reserve (0.8%); 0.4% of antibiotics remained unclassified. There was unexplained 2-fold variation in prescribing between hospitals within each AWaRe category, highlighting the potential for quality improvement. CONCLUSIONS: We have adapted the WHO AWaRe index to create a specific index for England. The AWaRe index provides high-level understanding of antibiotic prescribing. Subsequent to this process the England AWaRe index is now embedded into national antibiotic stewardship policy and incentivized quality improvement schemes.

Policy document on antimicrobial stewardship practices in India.

Antimicrobial resistance (AMR) in India has become a great threat because of high rate of infectious diseases. One of the key contributing factors is high antibiotic use due to poor prescription practices, self-medication, over-the-counter sale of drugs and lack of awareness. Antimicrobial stewardship programme (AMSP) have been proved to be successful in restraining sale and use of antibiotics to a large extent in many countries. An AMSP programme for a hospital is imperative for rational and evidence-based antimicrobial therapy. The ultimate aim is to improve patient outcomes, reduce emergence of bacterial resistance and ensure longevity of the existing antimicrobials. The primary goal of AMSP is to encourage cautious use of available antibiotics by training the healthcare workers and creating awareness. This article describes the strategies and recommendations for formulation of AMSP policy for India.

Practices, organisation, and regulatory aspects in advising on antibiotic prescription: the international ESCMID AntibioLegalMap survey.

PURPOSE: Giving advice about antibiotic prescription through dedicated consultations is a cornerstone of antibiotic stewardship programmes. Our objective was to explore practices, organisation, and regulatory requirements related to antibiotic advising. METHODS: We performed an international, exploratory, Internet-based, cross-sectional survey targeting infectious diseases and clinical microbiology specialists. It was disseminated through ESCMID and ESGAP networks. RESULTS: Answers from 830 participants (74 countries, 77% of participants from Europe) were collected. Consultations were mostly given on demand (81%, 619/764), while unsolicited consultations targeting specific conditions (e.g., positive blood culture) were less frequent (66%, 501/764). Consultations usually included indications on diagnostic work-up and follow-up (> 79%). Curbside consultations (i.e., without examining the patient) were reported by 82% (598/733) of respondents, mainly by phone (89%, 531/598). The referring physician was considered authorised not to follow the advice by 57% (383/676). Direct consultations (i.e., after examining the patient) were recorded in the medical file more frequently than curbside consultations (69%, 472/689 vs 35%, 206/592). Concerning legal liability, the majority of respondents considered that it is shared between the adviser and the referring physician, who, however, is considered primarily responsible. The advisers' liability was considered to be lower in cases of curbside and unrecorded consultations. Significant inter-countries and intra-country variability were identified, suggesting that the setting markedly influenced practices. CONCLUSION: Significant variability exists in the practice of antibiotic advising. This concerns both the organisation of care and how advisers perceive regulatory requirements. These elements must be taken into account when implementing antibiotic stewardship programmes and when training stewards.

Enlisting the support of trusted sources to tackle policy problems: The case of antimicrobial resistance.

Antimicrobial resistance represents one of the world's most pressing public health problems. Governments around the world have-and will continue to-develop policy proposals to deal with this problem. However, the capacity of government will be constrained by very low levels of trust in government. This stands in contrast to 'medical scientists' who are highly trusted by the public. This article tests to what extent trusted sources can alter attitudes towards a policy proposal to regulate the use of antibiotics. We find that respondents are much more likely to support a policy put forward by 'medical scientists.' This article provides some initial evidence that medical scientists could be used to gain support for policies to tackle pressing policy challenges such as AMR.