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.

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.

Effects of Antibiotic Cycling Policy on Incidence of Healthcare-Associated MRSA and Clostridioides difficile Infection in Secondary Healthcare Settings.

This quasi-experimental study investigated the effect of an antibiotic cycling policy based on time-series analysis of epidemiologic data, which identified antimicrobial drugs and time periods for restriction. Cyclical restrictions of amoxicillin/clavulanic acid, piperacillin/tazobactam, and clarithromycin were undertaken over a 2-year period in the intervention hospital. We used segmented regression analysis to compare the effect on the incidence of healthcare-associated Clostridioides difficile infection (HA-CDI), healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA), and new extended-spectrum ß-lactamase (ESBL) isolates and on changes in resistance patterns of the HA-MRSA and ESBL organisms between the intervention and control hospitals. HA-CDI incidence did not change. HA-MRSA incidence increased significantly in the intervention hospital. The resistance of new ESBL isolates to amoxicillin/clavulanic acid and piperacillin/tazobactam decreased significantly in the intervention hospital; however, resistance to piperacillin/tazobactam increased after a return to the standard policy. The results question the value of antibiotic cycling to antibiotic stewardship.

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.

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.

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.

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.

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.

Antimicrobial Stewardship in China: Systems, Actions and Future Strategies.

Antimicrobial resistance (AMR) has become a serious global public health crisis, and AMR control has consequently become a priority in all countries. Specifically, the incidence of various common multidrug-resistant bacteria is high, and there are multiple problems concerning the irrational use of antimicrobial drugs. In the past decade, China has established a relatively comprehensive management system and technical support framework for antimicrobial stewardship, including regulations, guidelines, networks for the surveillance of AMR and antimicrobial consumption, and professional personnel training. In addition, the Ministry of Health has carried out a special campaign to promote the proper clinical use of antibiotics in medical institutions, which significantly improved outcomes. The use of antibacterial drugs without indication and the consumption of antibiotics have been significantly reduced. In consideration of the factors that contribute to AMR, the structure of the healthcare system in China, and the need for long-term sustaining efforts to control AMR, the strategy of "two steps and two hands" must be implemented to contain AMR. The first step is to generally promote the rational use of antimicrobial agents in order to promptly curb the rising momentum of resistance with high pressure from the government. The second step requires sustainable professional work with the implementation of precise AMR control. The "first hand" refers to the government-oriented active establishment and optimization of the system and infrastructure of rational antibiotic use and AMR control. The "second hand" refers to the cultivation of professional teams to ensure the establishment and development of sustainable processes in AMR control.

Defensive medicine among antibiotic stewards: the international ESCMID AntibioLegalMap survey.

Objectives: To investigate fear of legal claims and defensive behaviours among specialists in infectious diseases (ID) and clinical microbiology (CM) and to identify associated demographic and professional characteristics. Methods: AntibioLegalMap was an international cross-sectional internet-based survey targeting specialists in ID and CM. Three variables were explored: fear of legal liability in antibiotic prescribing/advising on antibiotic prescription; defensive behaviours in antibiotic prescribing; and defensive behaviours in advising. A multivariable logistic regression analysis was performed to identify factors significantly associated with each of the three variables. Results: Eight hundred and thirty individuals from 74 countries participated. Only 0.4% (3/779) had any kind of condemnation for malpractice related to antibiotic prescription. Concerning the fear of liability, 21.2% (164/774) of respondents said they never worried, 45.1% (349/774) sometimes worried and 28.6% (221/774) frequently worried when prescribing/advising on antibiotic prescription. Being female, younger than or equal to 35 years and aware of previous cases of litigation were independently associated with fear. Most respondents (85.0%, 525/618) reported some defensive behaviour in antibiotic prescribing. These behaviours were independently associated with being younger than or equal to 35 years and sometimes or often worried about liability. Similarly, 76.4% (505/661) reported defensive behaviours in advising. These behaviours were associated with being sometimes or often worried about liability. The preferred measures to reduce fear and defensive behaviours were having local guidelines and sharing decisions through teamwork. Conclusions: A significant proportion of specialists in ID and CM reported some form of defensive behaviour in prescribing or advising to prescribe antibiotics. Defensive medicine should be considered when implementing antibiotic stewardship programmes.

Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care.

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy-one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty-four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified.

A Handshake From Antimicrobial Stewardship Opens Doors for Infectious Disease Consultations.

Implementation of a unique in-person pediatric antimicrobial stewardship program was associated with a significant increase in infectious disease consultations at a quaternary care children's hospital. This study demonstrates that antimicrobial stewardship programs support, and do not compete with, infectious disease programs.

Antimicrobial Stewardship in Inpatient Settings in the Asia Pacific Region: A Systematic Review and Meta-analysis.

BACKGROUND: An antimicrobial stewardship program (ASP) is one of the core elements needed to optimize antimicrobial use. Although collaboration at the national level to address the importance of ASPs and antimicrobial resistance has occurred in the Asia Pacific region, hospital-level ASP implementation in this region has not been comprehensively evaluated. METHODS: We conducted a systematic review and meta-analysis to assess the efficacy of ASPs in inpatient settings in the Asia Pacific region from January 2005 through March 2016. The impact of ASPs on various outcomes, including patient clinical outcomes, antimicrobial prescription outcomes, microbiological outcomes, and expenditure were assessed. RESULTS: Forty-six studies were included for a systematic review and meta-analysis. The pooled risk ratio for mortality from ASP before-after trials and 2-group comparative studies were 1.03 (95% confidence interval [CI], .88-1.19) and 0.69 (95% CI, .56-.86), respectively. The pooled effect size for change in overall antimicrobial and carbapenem consumption (% difference) was -9.74% (95% CI, -18.93% to -.99%) and -10.56% (95% CI, -19.99% to -3.03%), respectively. Trends toward decreases in the incidence of multidrug-resistant organisms and antimicrobial expenditure (range, 9.7%-58.1% reduction in cost in the intervention period/arm) were also observed. CONCLUSIONS: ASPs in inpatient settings in the Asia Pacific region appear to be safe and effective to reduce antimicrobial consumption and improve outcomes. However, given the significant variations in assessing the efficacy of ASPs, high-quality studies using standardized surveillance methodology for antimicrobial consumption and similar metrics for outcome measurement are needed to further promote antimicrobial stewardship in this region.

Obtaining antibiotics online from within the UK: a cross-sectional study.

Background: Improved antibiotic stewardship (AS) and reduced prescribing in primary care, with a parallel increase in personal internet use, could lead citizens to obtain antibiotics from alternative sources online. Objectives: A cross-sectional analysis was performed to: (i) determine the quality and legality of online pharmacies selling antibiotics to the UK public; (ii) describe processes for obtaining antibiotics online from within the UK; and (iii) identify resulting AS and patient safety issues. Methods: Searches were conducted for 'buy antibiotics online' using Google and Yahoo. For each search engine, data from the first 10 web sites with unique URL addresses were reviewed. Analysis was conducted on evidence of appropriate pharmacy registration, prescription requirement, whether antibiotic choice was 'prescriber-driven' or 'consumer-driven', and whether specific information was required (allergies, comorbidities, pregnancy) or given (adverse effects) prior to purchase. Results: Twenty unique URL addresses were analysed in detail. Online pharmacies evidencing their location in the UK ( n = 5; 25%) required a prescription before antibiotic purchase, and were appropriately registered. Online pharmacies unclear about the location they were operating from ( n = 10; 50%) had variable prescription requirements, and no evidence of appropriate registration. Nine (45%) online pharmacies did not require a prescription prior to purchase. For 16 (80%) online pharmacies, decisions were initially consumer-driven for antibiotic choice, dose and quantity. Conclusions: Wide variation exists among online pharmacies in relation to antibiotic practices, highlighting considerable patient safety and AS issues. Improved education, legislation, regulation and new best practice stewardship guidelines are urgently needed for online antibiotic suppliers.

Outcomes of multisite antimicrobial stewardship programme implementation with a shared clinical decision support system.

Background: Studies evaluating antimicrobial stewardship programmes (ASPs) supported by computerized clinical decision support systems (CDSSs) have predominantly been conducted in single site metropolitan hospitals. Objectives: To examine outcomes of multisite ASP implementation supported by a centrally deployed CDSS. Methods: An interrupted time series study was conducted across five hospitals in New South Wales, Australia, from 2010 to 2014. Outcomes analysed were: effect of the intervention on targeted antimicrobial use, antimicrobial costs and healthcare-associated Clostridium difficile infection (HCA-CDI) rates. Infection-related length of stay (LOS) and standardized mortality ratios (SMRs) were also assessed. Results: Post-intervention, antimicrobials targeted for increased use rose from 223 to 293 defined daily doses (DDDs)/1000 occupied bed days (OBDs)/month (+32%, P < 0.01). Conversely, antimicrobials targeted for decreased use fell from 254 to 196 DDDs/1000 OBDs/month (-23%; P < 0.01). These effects diminished over time. Antimicrobial costs decreased initially (-AUD$64551/month; P < 0.01), then increased (+AUD$7273/month; P < 0.01). HCA-CDI rates decreased post-intervention (-0.2 cases/10 000 OBDs/month; P < 0.01). Proportional LOS reductions for key infections (respiratory from 4.8 to 4.3 days, P < 0.01; septicaemia 6.8 to 6.1 days, P < 0.01) were similar to background LOS reductions (2.1 to 1.9 days). Similarly, infection-related SMRs (observed/expected deaths) decreased (respiratory from 1.1 to 0.75; septicaemia 1.25 to 0.8; background rate 1.19 to 0.90. Conclusions: Implementation of a collaborative multisite ASP supported by a centrally deployed CDSS was associated with changes in targeted antimicrobial use, decreased antimicrobial costs, decreased HCA-CDI rates, and no observable increase in LOS or mortality. Ongoing targeted interventions are suggested to promote sustainability.

Policy text analysis of antimicrobial resistance governance in China: A focus on national-level policies.

OBJECTIVE: To explore the structure and characteristics of China's national policies regarding antimicrobial resistance (AMR) governance. METHOD: This research constitutes a quantitative content analysis of AMR policies issued by the central government from 2004 to 2023. A systematic search identified 112 policy documents, which were analysed using a three-dimensional framework. This framework included policy objectives, policy instruments (The supply-focused instrument aims to promote rational and prudent antibiotic prescriptions. The demand-focused instrument affects consumer use of antibiotics, either directly or indirectly. The environment-focused instrument provides a favourable and systematic policy environment for the prudent use of antibiotics.) and policy evolvement. Sub-themes under the framework were identified through a deductive process, followed by descriptions of frequency distributions of the sub-themes and categories. RESULTS: The majority of policy documents originated from individual governmental departments, with only 8 (7.14%) being jointly issued. The National Health Commission (NHC) remained the predominant policy maker, issuing 56 (48.21%) policies. A clear preference emerged for utilizing environment-focused policy instruments (69.70%), compared with the demand-focused (18.45%) and supply-focused (11.85%) instruments. 'Optimizing the use of antimicrobial medicines' ranked on top of the policy objectives, with 185 (31.25%) citations extracted across 74 (30.58%) policy documents. In addition to increasing numbers of policies over the three stages (2004-2011, 2012-2015, 2016-2023) of development, the use of various instruments became more comprehensive and balanced in the third stage. CONCLUSIONS: AMR governance has become increasingly comprehensive in China, despite a deficit in inter-sectoral collaborations. A whole-of-government approach is required to maximize the value of various policy initiatives.

How Might Antibiotic Stewardship Programs Influence Clinicians' Autonomy and Organizations' Liability?

Federal and state governments mandate some health care organizations to implement antibiotic stewardship programs (ASPs). Some early adopters developed model ASPs that have helped set industry standards; other benchmarks will likely be forged in subsequent regulation, legislation, and jurisprudence. This article considers how ASP designs can affect professional autonomy, especially of frontline antibiotic stewards who are usually physicians and pharmacists. This article also considers how ASP development and implementation might influence standards of care and malpractice liability.

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.