Prescribing antibiotics prudently-A survey of policy implementation drivers among physicians and veterinarians.

Background: As the antimicrobial resistance (AMR) problem accelerates, humans and animals are suffering from the consequences of infections with diminishing antimicrobial treatment options. Within the One Medicine and One Health mandate, which denotes a collaborative, multisectoral, and transdisciplinary approach to improve medicine and health across human and animal sectors, we investigate how human and veterinary medical practitioners apply their medical and policy knowledge in prescribing antimicrobials. Different regions and locations establish different intermediary policies and programs to support clinicians in that pursuit. In Hong Kong, there are locally adapted programs at governance and clinical levels in the human medical field. However, there is no locally adapted veterinary antibiotic prescription guideline or stewardship program, and veterinarians adopt overseas or international professions' antimicrobial use guidelines. Such a policy environment creates a natural experiment to compare local policy implementation conditions and clinicians' knowledge, perception, and practice. Method: We construct the investigative survey tool by adaptation of Knowledge, Attitude, and Practice (KAP) and Capacity, Opportunity, and Motivation-Behavior (COM-B) models. We identify, compare and contrast factors that influence clinicians' antimicrobial prescription behavior. The factors are considered both intrinsically, such as personal attributes, and extrinsically, such as societal and professional norms. Findings: The absence of locally adopted antimicrobial guidelines influences AMR stewardship program implementation in local Hong Kong veterinary community. As medical allies, physicians and veterinarians share similar demographic influence, organization considerations and perception of public awareness. Both cohorts prescribe more prudently with more years-in-practice, time available to communicate with patients or caretakers, and public awareness and support.

Why prescribe antibiotics? A systematic review of knowledge, tension, and motivation among clinicians in low-, middle- and high-income countries.

Medical professionals such as physicians and veterinarians are responsible for appropriate antimicrobial prescription (AMP) and use. Although seemingly straightforward, the factors influencing antibiotic prescription, a category of antimicrobials, are complex. Many studies have been conducted in the past two decades on this subject. As a result, there is a plethora of empirical evidence regarding the factors influencing clinicians' AMP practices. AIM: A systematic review of AMR studies on AMP was conducted, condensing findings according to a combination of the Knowledge, Attitude, and Practice (KAP) and Capacity, Opportunity, Motivation-Behavior (COM-B) models. Review findings were then synthesized and analyzed for policy implementation according to the Consolidated Framework for Implementation Research (CFIR). DESIGN AND METHODOLOGY: A systematic literature review was conducted according to PRISMA guidelines to identify peer-reviewed papers indexed in pre-determined medical science, social sciences, and humanities databases that apply the KAP model in their investigations. Antimicrobial prescription factors were compared and contrasted among low- and middle-income countries (LMICs) and high-income countries (HICs). FINDINGS: The KAP model is a heuristic and structured framework for identifying and classifying respondents' knowledge. However, other than medical knowledge, factors that influence prescription decision-making can be expanded to include attitudes, perception, personal affinities, professional circumstances, relational pressure, and social norms.

Longitudinal monitoring reveals the emergence and spread of blaGES-5-harboring carbapenem-resistant Klebsiella quasipneumoniae in a Hong Kong hospital wastewater discharge line.

Testing hospital wastewater (HWW) is potentially an effective, long-term approach for monitoring trends in antimicrobial resistance (AMR) patterns in health care institutions. Over a year, we collected wastewater samples from the clinical and non-clinical sites of a tertiary hospital and from a downstream wastewater treatment plant (WWTP). We focused on the extent of carbapenem resistance among Enterobacteriaceae isolates given their clinical importance. Escherichia coli and Klebsiella spp. were the most frequently isolated Enterobacteriaceae species at all sampling sites. Additionally, a small number of isolates belonging to ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), except K. pneumoniae, were detected. Of the 232 Klebsiella spp. isolates, 100 (43.1 %) were multi-drug resistant (MDR), with 46 being carbapenem-resistant. Most of these carbapenem-resistant isolates were K. quasipneumoniae (CRKQ) (n = 44). All CRKQ isolates were isolated from the wastewater of a clinical site that includes intensive care units, which also yielded significantly more multi-drug resistant isolates compared to all other sampling sites. Among the CRKQ isolates, blaGES-5 genes (n = 42) were the primary genetic determinant of carbapenem resistance. Notably, three different CRKQ isolates, collected within the same month in HWW and the influent and effluent flow of the WWTP, shared >99 % sequence similarity between their blaGES-5 genes and between their flanking regions and upstream integron-integrase region. The influent isolate was phylogenetically close to K. quasipnuemoniae isolates from wastewater collected in Japan. Its blaGES-5 gene and surrounding sequences were > 99 % identical to blaGES-24 genes found in the Japanese isolates. Our results suggest that testing samples from sites located closer to hospitals could support antibiotic stewardship programs compared to samples collected further downstream. Moreover, testing samples collected regularly from WWTPs may reflect the local and global spread of pathogens and their resistances.

Subsidized veterinary extension services may reduce antimicrobial resistance in aquaculture.

Antibiotic use in aquaculture has become very controversial vis-à-vis driving antimicrobial resistance (AMR) in aquatic bacterial populations. The AMR trends in fish pathogens in Hong Kong over a four-year period suggests that providing small stakeholder farmers with free veterinary advice on fish health issues and treatments, as well as subsidized quality-assured medicines, likely reduced AMR. We observed a dramatic reduction in the proportion of bacteria resistant to oxolinic acid, oxytetracycline, and florfenicol on local aquaculture farms between 2018 and 2021. These decreases coincided with either a change in antibiotic use practices on farms (i.e. with oxytetracycline), or the reduction in the use of specific drugs (i.e. oxolinic acid and florfenicol). We did not observe a similar decline in the resistance pattern to commonly used antibiotics in human medicine in the same fish bacteria. Resistance to these products, which were unlikely to be used by the farmers in our study, was very high. Our finding suggests that both human and veterinary use of antibiotics in Hong Kong may have an influence on the AMR of bacteria in the aquatic environment.

One Health Surveillance of Antimicrobial Use and Resistance: Challenges and Successes of Implementing Surveillance Programs in Sri Lanka.

BACKGROUND: Sri Lanka is a low-income country, as defined by the World Bank. The country suffered further economic downturn during the COVID-19 pandemic. This situation adversely affected the prioritization of policies and programs around healthcare and public health. In particular, inflation, fuel prices, and shortage of food supplies increased struggles to implement antimicrobial resistance (AMR) programs. However, in the long run, it is crucial to gather data and evidence to plan AMR policies and track interventions. (1) Aim: To establish and reiterate the importance of prioritizing AMR programs in the One Health framework, the Fleming Fellows collected and studied antimicrobial use/consumption (AMU/AMC) and resistance (AMR) in humans, food-producing animals, and the environment. (2) Methods: A systematic and cross-sectional study was conducted between 2019 and 2021. By way of coordinating an AMU/AMC and AMR prevalence study across six agencies from human health and food-producing animal sectors, the authors established a field epidemiology study, laboratory testing, and data processing at their institutions. AMU/AMC patterns were surveyed using questionnaires and interviews, while AMR samples were collected for antibiotic susceptibility tests and genomic tests. Samples were tested for phenotypic and genotypic resistance. (3) Results: In human samples, resistance was highest to beta-lactam antibiotics. In non-human samples, resistance was highest to erythromycin, a highest-priority, critically important antibiotic defined by the World Health Organization. From government records, tylosin was sold the most in the food-producing animal sector. (4) Conclusions: Sri Lanka AMU and AMR trends in human and non-human sectors can be ascertained by a One Health framework. Further coordinated, consistent, and sustainable planning is feasible, and can help implement an AMU/AMR surveillance system in Sri Lanka.

Experiences with COVID-19 case investigation and contact tracing: A qualitative analysis.

Case investigation and contact tracing (CI/CT) is a critical part of the public health response to COVID-19. Individuals' experiences with CI/CT for COVID-19 varied based on geographic location, changes in knowledge and guidelines, access to testing and vaccination, as well as demographic characteristics including age, race, ethnicity, income, and political ideology. In this paper, we explore the experiences and behaviors of adults with positive SARS-CoV-2 test results, or who were exposed to a person with COVID-19, to understand their knowledge, motivations, and facilitators and barriers to their actions. We conducted focus groups and one-on-one interviews with 94 cases and 90 contacts from across the United States. We found that participants were concerned about infecting or exposing others, which motivated them to isolate or quarantine, notify contacts, and get tested. Although most cases and contacts were not contacted by CI/CT professionals, those who were reported a positive experience and received helpful information. Many cases and contacts reported seeking information from family, friends, health care providers, as well as television news and Internet sources. Although participants reported similar perspectives and experiences across demographic characteristics, some highlighted inequities in receiving COVID-19 information and resources.

Continuity of Care Advocate Model (CCAM): Healthcare Workers' Perspectives on Quality Stroke Care at an Acute Unit, Rehabilitation Center and Community Rehabilitation Program in Singapore.

Physicians, nurses, social workers, and allied health professionals including physiotherapists and occupational therapists play important roles as they work closely with stroke survivors to improve functional independence in daily activities and quality of life. Yet, in Singapore little is known about their perspectives on what constitute quality stroke care based on their clinical experiences. In this project, our qualitative interviews with 15 healthcare workers at a major stroke center in the country yielded a Continuity of Care Advocate Model (CCAM) to help us better understand our participants' experience-based perspectives on quality stroke care. We found that CCAM, constructed based on the perspectives of HCWs across a stroke care continuum, is a holistic model of quality stroke care which prioritizes support for patients and their families throughout the patient's health trajectory. We conclude by discussing how this model is aligned with and differs from current research on definitions of care continuity.

Antimicrobial Resistance Policy Protagonists and Processes-A Qualitative Study of Policy Advocacy and Implementation.

Antimicrobial resistance (AMR) fundamentally weakens societal foundations economically and in health care. The development of well-considered policies against AMR is important. However, in many places, AMR policy implementation remains elusive. This study aims to identify enablers and deterrents as well as processes and conditions in AMR policy advocacy. It also aims to identify AMR implementation conditions where AMR national policies are adopted and, to a certain extent, formulated and implemented. This study adopts qualitative research methodology and applies the Grounded Theory Framework to identify thematic findings from interviews conducted in China, Japan, Norway, the United Kingdom (UK), and the United States of America (US). It was identified that AMR policy protagonists are critical to filtering AMR issues and identifying policies "fit to prioritize" and "fit to implement". They have helped move policy prioritization needles in the UK and the US and engaged in diplomatic efforts in the UK. In these cases, no clientelism was considered. In the US, protagonists who talked to the right decision-makers in the right office at the right time both moved AMR issues from individuals to institutional agenda and from social norms to policy agenda. To conclude, there are three thematic policy conditions that are significant to AMR policy advocacy and implementation: committed personal championship, institutionalization of policies, and social norms facilitate AMR policy advocacy and implementation.

A Retrospective Study of Antimicrobial Resistant Bacteria Associated with Feline and Canine Urinary Tract Infection in Hong Kong SAR, China-A Case Study on Implication of First-Line Antibiotics Use.

Urinary tract infection (UTI) is a common clinical diagnosis for which empirical antibiotics are used in veterinary medicine. For veterinarians, the description of canine and feline antibiograms can help with making prudent use decisions and guideline formulation. For public health officers and epidemiologists, a urinary antibiogram overview helps track and trend antimicrobial resistance (AMR). There is currently a knowledge gap in AMR prevalence associated with urinary tract infection in feline and canine patients and the resistance percentage of these microbes against some of the over-the-counter antibiotics available to local pet owners. This study has two aims. First, it aims to investigate the frequency of the bacteria and bacterial-resistance pattern in urine samples obtained from feline and canine patients. Second, it aims to determine the resistance of Escherichia coli (E. coli), the most frequently isolated bacteria, to first-line antibiotics. Results: We identified the five most-frequently isolated bacterial species and determined these isolates' antibiotic sensitivity and resistance. The most-frequently isolated bacteria in feline and canine patients was Escherichia coli (E. coli). E. coli was identified, on average, in 37.2% of canine and 46.5% of feline urine samples. Among feline urinary samples, Enterococcus (14.7%) and Staphylococcus (14.5%) spp. were isolated more frequently, followed by Pseudomonas (4.8%) and Klebsiella (5.2%) spp. (). In canine samples, Proteus (17.9%) and Staphylococcus (13.2%) spp. were isolated more frequently, followed by Enterococcus (10.0%) and Klebsiella (8.59%) spp. Among these isolates, 40 to 70% of Staphylococcus spp. bacterial isolates from feline and canine patients were resistant to amoxicillin and ampicillin. During the three-year study period, among canine patients, 10 to 20% of Staphylococcus spp. bacterial isolates were resistance to fluoroquinolones, other quinolones, and third-generation cephalosporins. Among feline patients, 10% of Staphylococcus spp., 15 to 20% of E. coli, 50 to 60% of Klebsiella spp., and 90% of Pseudomonas spp. were resistant to cefovecin, a commonly used antibiotic.

Ventilatory neural drive in chronically hypercapnic patients with COPD: effects of sleep and nocturnal noninvasive ventilation.

Sleep brings major challenges for the control of ventilation in humans, particularly the regulation of arterial carbon dioxide pressure (P aCO2 ). In patients with COPD, chronic hypercapnia is associated with increased mortality. Therefore, nocturnal high-level noninvasive positive-pressure ventilation (NIV) is recommended with the intention to reduce P aCO2 down to normocapnia. However, the long-term physiological consequences of P aCO2 "correction" on the mechanics of breathing, gas exchange efficiency and resulting symptoms (i.e. dyspnoea) remain poorly understood. Investigating the influence of sleep on the neural drive to breathe and its translation to the mechanical act of breathing is of foremost relevance to create a solid rationale for the use of nocturnal NIV. In this review, we critically discuss the mechanisms by which sleep influences ventilatory neural drive and mechanical consequences in healthy subjects and hypercapnic patients with advanced COPD. We then discuss the available literature on the effects of nocturnal NIV on ventilatory neural drive and respiratory mechanics, highlighting open avenues for further investigation.

A Universal LC-MS/MS Method for Simultaneous Detection of Antibiotic Residues in Animal and Environmental Samples.

Detecting and monitoring the usage of antibiotics is a critical aspect of efforts to combat antimicrobial resistance. Antibiotic residue testing with existing LC-MS/MS methods is limited in detection range. Current methods also lack the capacity to detect multiple antibiotic residues in different samples simultaneously. In this study, we demonstrate a methodology that permits simultaneous extraction and detection of antibiotic residues in animal and environmental samples. A total of 30 different antibiotics from 13 classes could be qualitatively detected with our methodology. Further study to reduce analytes' matrix effect would allow for quantification of antibiotic residues.

Unpacking multi-level governance of antimicrobial resistance policies: the case of Guangdong, China.

Against the backdrop of universal healthcare coverage and pre-existing policies on antimicrobial use, China has adopted a state-governed, multi-level, top-down policy governance approach around an antimicrobial resistance (AMR) national action plan (NAP). The Plan relies on tightening control over antimicrobial prescription and use in human and animal sectors. At the same time, medical doctors and veterinarians operate in an environment of high rates of infectious diseases, multi-drug resistance and poor livestock husbandry. In exploring the way that policy responsibilities are distributed, this study aims to describe how Guangdong as a province adopts national AMR policies in a tightly controlled public policy system and an economy with high disparity. We draw on an analysis of 225 AMR-relevant Chinese policy documents at the national and sub-national levels. We adopt a multi-level governance perspective and apply a temporal sequence framework to identify and analyse documents. To identify policy detail, we conducted keyword analysis using the Consolidated Framework for Implementation Research (CFIR) on policies that conserve antimicrobials. We also identify pre-existing medical and public policies associated with AMR. Our findings highlight the emphasis and policies around antimicrobial use regulation to address AMR in China.

From guide to guard-activation mechanism of the stress-sensing chaperone Get3.

Oxidative stress conditions can cause ATP depletion, oxidative protein unfolding, and potentially toxic protein aggregation. To alleviate this proteotoxic stress, the highly conserved yeast protein, Get3, switches from its guiding function as an ATP-dependent targeting factor for tail-anchored proteins to its guarding function as an ATP-independent molecular chaperone that prevents irreversible protein aggregation. Here, we demonstrate that activation of Get3's chaperone function follows a tightly orchestrated multi-step process, centered around the redox status of two conserved cysteines, whose reactivity is directly controlled by Get3's nucleotide-binding state. Thiol oxidation causes local unfolding and the transition into chaperone-active oligomers. Vice versa, inactivation requires the reduction of Get3's cysteines followed by ATP-binding, which allows the transfer of bound client proteins to ATP-dependent chaperone systems for their effective refolding. Manipulating this fine-tuned cycle of activation and inactivation in yeast impairs oxidative stress resistance and growth, illustrating the necessity to tightly control Get3's intrinsic chaperone function.

Understanding the Implementation of Antimicrobial Policies: Lessons from the Hong Kong Strategy and Action Plan.

In 2017, the Hong Kong Strategy and Action Plan on Antimicrobial Resistance 2017-2022 (HKSAP) was announced with the aim of tackling the growing threat of antimicrobial resistance (AMR) in Hong Kong. However, little is known about how the planned activities have been implemented. In this study, we examine the status of implementation of the HKSAP using the Smith Policy Implementation Process Model. Semi-structured interviews with 17 informants found that important achievements have been made, including launching educational and training activities targeting the public, farmers, and healthcare professionals; upgrading the AMR surveillance system; and strengthening AMR stewardship and infection control. Nevertheless, participants also identified barriers to greater implementation, such as tensions across sectors, ongoing inappropriate drug use and prescription habits, insufficient human and technical resources, as well as a weak accountability framework. Environmental factors such as the COVID-19 pandemic also affected the implementation of HKSAP. Our study indicated that expanding engagement with the public and professionals, creating a collaborative environment for policy implementation, and building a well-functioning monitoring and evaluation system should be areas to focus on in future AMR policies.

Comparison of Delay in Tuberculosis Diagnosis Between Migrants and Local Residents in an Eastern County of China: An Analysis of the Electronic Data Between 2015 and 2019.

Introduction: China continues to rank among one of the countries with the highest number of tuberculosis (TB) cases globally. Migrants are a particularly at-risk subgroup for TB and pose a challenge for case management in contemporary China. The early diagnosis and treatment of patients with TB are pivotal for effective TB control. This study investigates the delay in the TB diagnosis of migrants as compared with residents, to provide an evidence base for improved case detection and the better management of migrant patients with TB. Materials and Methods: The data was collected from the Tuberculosis Information Management System (TBIMS) (2015-2019) in an eastern county of China. The total diagnostic delay, consisting of patient delay and health system delay, is defined as the interval between the onset of TB symptoms and the confirmation of TB diagnosis in the designated TB hospital. The comparison of the delay in the TB diagnosis between migrants and residents was conducted using a Mann-Whitney U-test and chi-square test. The difference in the delay curves between these two groups was examined using a log-rank test. Results: Of 2,487 patients with TB, 539 (22%) were migrants. The migrants tended to be younger, presented with less severe conditions, received an initial diagnosis at prefectural and above-level hospitals. Compared with the local patients with TB, the migrant patients with TB had a longer median total diagnostic delay (30 vs. 9, P = 0.000) and a higher proportion of patients with this delay >28 days (52 vs. 13%, P = 0.000). Similarly, the migrant patients with TB also had a longer median patient delay (13 vs. 9, P = 0.000) and a higher proportion of patients with this delay >14 days (47 vs. 30%, P = 0.000), longer median health system delay (9 vs. 0, P = 0.000), and a higher proportion of patients with this delay >14 days (42 vs. 0.5%, P = 0.000) than the local patients with TB. The survival curves of delay showed that the longer the time interval was, the more likely the migrant patients with TB were to be diagnosed (P < 0.05). Conclusions: Diagnosis is significantly delayed among migrant patients with TB. Our study highlights the importance of early screening and diagnosis for TB especially among migrants, to improve access and ensure better management for all patients with TB.

Upholding veterinary services as a pillar of one health in Myanmar.

Veterinary service is one of the pillars to restore One Health in Myanmar. In the immediate future, international support provided to Myanmar can relieve food shortage and some humanitarian crises. In the long run, societal trauma from the military coup and violence, infrastructure breakdown, and economic downturn complicated by the COVID-19 pandemic will make recovery of the nation harder. While the building blocks to achieve peace and humanitarianism are long and complicated, part of the interim solution is to restore Myanmar veterinary services. The restoration will ease food scarcity in the short-run, reduce sylvatic and zoonotic infection risks and re-capitalise societal infrastructure building in the long-run. Myanmar society cannot rebuild on its own-it needs international and national support to facilitate peace and humanitarianism.

National action to combat AMR: a One-Health approach to assess policy priorities in action plans.

Little is known about the overall trend and prioritisations of past and current antimicrobial resistance (AMR) policies. Here we introduce a quantitative method to analyse AMR policies. The AMR-Policy Analysis Coding Toolkit (AMR-PACT) uses several categorical variables. Thirteen AMR action plans from five countries (China, Japan, Norway, the UK and the USA) were used to develop the tool and identify possible values for each variable. The scope and capability of AMR-PACT is demonstrated through the 2015 WHO's Global Action Plan and 2017 Hong Kong AMR Action Plan (HKAP). Majority of policies were aimed at either human or animal sector with less attention given to the environment, plant or food sector. Both plans shared the same two strategic focus areas, namely the conservation of antibiotics and the improved surveillance of resistance. There were no policies dedicated to improving access to antibiotics in the HKAP. These empirical results provide useful insights into the priorities and gaps of AMR policies. The method proposed here can help understand countries' priorities regarding AMR, support the creation of AMR policy database and foster innovative policymaking.