Antimicrobial Resistance Stewardship Research Articles

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

BackgroundAs 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. MethodWe construct the investigative survey tool by adaptation of Knowledge, Attitude, and Practice (KAP) and Capacity, Opportunity, and Motivation-Behavior (COMB) 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. FindingsThe 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.

Antimicrobial resistance in ocular infection: A review.

Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin-resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up-to-date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS.

Antimicrobial stewardship hindered by inadequate biosecurity and biosafety practices, and inappropriate antibiotics usage in poultry farms of Nepal-A pilot study.

Nepal's poultry industry has experienced remarkable growth in the last decade, but farm biosafety and biosecurity measures are often overlooked by farmers. As a result, farms often suffer from sporadic and regular outbreaks of many diseases, impacting production and creating public health challenges. Poor management practices, including overuse of antibiotics for prophylaxis and therapeutics, can enhance the spread of poultry diseases by propagating antimicrobial resistance (AMR) that is threatening poultry and human health. We assessed biosafety, biosecurity risks and AMR stewardship in sixteen poultry farms located in four districts: Ramechhap, Nuwakot, Sindhupalchowk, and Kavre. Risk assessment and AMR stewardship evaluation questionnaires were administered to formulate biosafety and biosecurity compliance matrix (BBCM). Risk assessment checklist assessed facility operations, personnel and standard operating procedures, water supply, cleaning and maintenance, rodent/pest control and record keeping. Oral and cloacal samples from the poultry were collected, pooled, and screened for eight poultry pathogens using Polymerase Chain Reaction (PCR) tests. Based on BBCM, we identified the highest BBCM score of 67% obtained by Sindhupalchowk farm 4 and the lowest of 12% by Kavre farm 3. Most of the farms (61.6%) followed general poultry farming practices, only half had clean and well-maintained farms. Lowest scores were obtained for personnel safety standard (42.4%) and rodent control (3.1%). At least one of the screened pathogens were detected in all farms. Mycoplasma gallisepticum was the most common pathogen detected in all but three farms, followed by Mycoplasma synoviae. More than half of the farmers considered AMR a threat, over 26% of them used antibiotics as a preventive measure and 81% did not consider withdrawal period for antibiotics prior to processing of their meat products. Additionally, antibiotics classified as "Watch" and "Restrict" by the WHO were frequently used by the farmers to treat bacterial infections in their farms.

Between superimposition and local initiatives: Making sense of ‘implementation gaps’ as a governance problem of antimicrobial resistance

Mitigating antimicrobial resistance (AMR) is a global imperative. Part of this effort is the translation of the Global Action Plan into National Action Plans on AMR (NAPs-AMR). However, effective implementation of these plans remains a governance challenge worldwide.This study aims to explore the apparent implementation gap as a governance problem in Austria by examining the situated perspectives of key experts and stakeholders involved in AMR-related policy and practice. Data were collected through semi-structured qualitative interviews, a focus group discussion, and participation in various symposia on AMR. Data analysis revealed key themes the experts have identified as decisive factors shaping AMR governance, which they perceive as insufficient. These include: the absence of a binding legal framework, incomplete and lacking AMR data, low risk perception, lack of funding mechanisms, and absence of an incentive system for people working in AMR stewardship.The interpretation of these findings suggests policy fragmentation, scattered responsibilities, agenda conformity and a lack of symbolic and material recognition as central features that impede a comprehensive, sustainable and effective AMR-related governance. These insights highlight a tension between local efforts to precipitate longer-term adaptations to prepare for and mitigate effectively AMR on the one hand, and the current approach of ‘superimposing’ reforms onto existing institutional structures. Effective and sustainable measures to address AMR require a fundamental restructuring process of institutional responsibilities, professional routines, and social practices to prioritize AMR stewardship as a guiding principle.

Large-scale questionnaire survey of parents and guardians on antimicrobial resistance using group health checkups for infants and toddlers in Japan

BackgroundIt is important to improve the knowledge of antimicrobial resistance (AMR) among parents and guardians, to promote AMR stewardship in pediatrics. However, a large-scale survey on parents' knowledge and awareness of AMR has not yet been conducted in Japan. Furthermore, the current status of knowledge and awareness is unknown. Infant and toddler health checkups are large-scale administrative activities that approximately all children and their parents undergo in Japan. Therefore, we conducted a knowledge and awareness survey using a questionnaire during the group health checkups. MethodsAll parents and guardians who participated in the group health checkups (4-month, 1.5-year, and 3-year) in Chiba City during the year were targeted. Parents' knowledge and awareness of AMR and their wishes for future information on AMR were surveyed using a one-choice questionnaire. ResultsThe questionnaire collection rate was 87.5% (16,663/19,047), and the valid response rate was 77.0% (14,674/19,047). Of the parents, 37.2% answered that "antibiotics are not effective for colds." However, 58.9% answered that they "had never heard of the drug-resistant bacteria."While 8.3% of parents answered that they "sometimes want my child to be prescribed antibiotics even if the doctor deemed it unnecessary," 46.1% of parents answered that "they were unaware of whether their children were prescribed antimicrobials." ConclusionsKnowledge and awareness of AMR among parents in Japan are inadequate, and there is room for improvement. Continuous awareness-raising activities combining multiple methods are needed in the future.

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.

P10 Rapid capture of uropathogenic bacteria and on-chip determination of antimicrobial resistance

BackgroundUrinary tract infection (UTI) is one of the most common bacterial infections responsible for increased annual incidence of antimicrobial resistance (AMR) cases. Clinical diagnosis of UTI AMR relies heavily on conventional urine culture and antibiotic susceptibility testing (AST) which has a turnaround time of ∼3 days. Often, irrespective of the infection status, antibiotics are prescribed to patients even before the test results are available, leading to non-judicious use of antibiotics. Over the years, several technologies have been developed for the rapid detection and diagnosis of UTI AMR, however, most of them are limited to traditional microbiological techniques and large laboratory equipment that are not readily available in low-to-middle income countries (LMICs). To address these diagnostic limitations, we are developing a rapid and affordable UTI-AMR diagnostic microfluidic device that is clinical friendly aimed at improving UTI management and AMR stewardship.ResultsOur device enables the flow of a large volume of urine specimens for the capture/enrichment of uropathogenic bacteria and determination of AST via a porous membrane that is augmented with a multifunctional polymer-based material. Important objectives for the development of UTI AMR diagnostic microfluidic device are: (i) development of a multifunctional polymer-based material; and (ii) validation of UTI AMR diagnostic device. We have successfully developed a polysaccharide-based platform to (i) selectively capture uropathogenic bacteria from urine specimen by immobilizing concanavalin A (con A) lectin as bacterial capture agent on the polymer surface via chemical modification; (ii) encapsulate and release bacterial nutrient media and antibiotics for AST; and (iii) detect AST via encapsulation of bacterial growth indicator. In addition, we have also determined the development of methacrylate-based and acrylamide-based synthetic polymer-based material for our application. Further, we have demonstrated the uniform augmentation of the polysaccharide-based polymer onto porous membrane via dip-coating technique for on-chip bacterial capture/enrichment and AST in fluid (urine) flow conditions. The porous membrane is a conducting material which enables us to perform electrochemical measurements such as impedance spectroscopy that accelerates the detection process of antibiotic susceptibility. As a proof-of-concept, we have determined the capture of biosafety level I Escherichia coli expressing kanamycin resistance gene on chemically surface modified polysaccharide-based polymer containing con A and the antibiotic susceptibility of captured bacteria against different antibiotics with and without the porous membrane. We have quantitatively determined the limit of detection of E. coli on multifunctional polysaccharide-based polymer material.ConclusionsThe utility of the UTI AMR microfluidic device in clinical settings enables clinicians to make informed decisions on the most appropriate antibiotic for treatment in less than a day. Integration of impedance spectroscopy will further accelerate the detection by significantly reducing the time of detection. Further, the device allows for off-chip analysis by retrieving the captured uropathogenic bacteria to perform high throughput sequencing for identifying AMR genetic determinants. Therefore, with the ability to selectively capture uropathogenic bacteria and determine AST in a short time, our technology has the potential to overcome some of the current limitations in UTI AMR diagnostics.

Antimicrobial Resistance and Environmental Health: A Water Stewardship Framework for Global and National Action.

Antimicrobial resistance (AMR) is a global health crisis that affects all life on Earth. In 2015, the World Health Organization developed guidance to combat AMR in accordance with a One Health framework considering human, animal, and environment sectors of planetary health. This study reviewed global guidance and 25 National Action Plans to evaluate thematic priorities in One Health AMR approaches using a novel framework that additionally facilitated the identification of water-related stewardship gaps, as water resources are recognized as the primary environmental AMR reservoir and dissemination pathway. This review found that global and national stewardship primarily focuses on mitigating antibiotic use in the human and animal sectors, overlooking environmental drivers, particularly diverse environmental waters. The findings of this study highlight the need to broaden the scope of water-related AMR concerns beyond water, sanitation, and hygiene (WASH) infrastructure for water supply and wastewater treatment, and account for environmental waters in AMR development and dissemination, particularly in low-income countries where half a billion people rely on environmental waters to meet daily needs. Equitably accounting for water environments, supplies, and waste in AMR prevention, mitigation, surveillance, and innovation can significantly enhance the integration of environmental objectives in One Health AMR stewardship.

National Antibiotics Utilization Trends for Human Use in Tanzania from 2010 to 2016 Inferred from Tanzania Medicines and Medical Devices Authority Importation Data.

Antimicrobial use (AMU) is one of the major drivers of emerging antimicrobial resistance (AMR). The surveillance of AMU, which is a pillar of AMR stewardship (AMS), helps devise strategies to mitigate AMR. This descriptive, longitudinal retrospective study quantified the trends in human antibiotics utilization between 2010 and 2016 using data on all antibiotics imported for systemic human use into Tanzania’s mainland. Regression and time series analyses were used to establish trends in antibiotics use. A total of 12,073 records for antibiotics were retrieved, totaling 154.51 Defined Daily Doses per 1000 inhabitants per day (DID), with a mean (±standard deviation) of 22.07 (±48.85) DID. The private sector contributed 93.76% of utilized antibiotics. The top-ranking antibiotics were amoxicillin, metronidazole, tetracycline, ciprofloxacin, and cefalexin. The DIDs and percentage contribution of these antibiotics were 53.78 (34.81%), 23.86 (15.44), 20.53 (13.29), 9.27 (6.0) and 6.94 (4.49), respectively. The time series model predicted a significant increase in utilization (p-value = 0.002). The model forecasted that by 2022, the total antibiotics consumed would be 89.6 DIDs, which is a 13-fold increase compared to 2010. Government intervention to curb inappropriate antibiotics utilization and mitigate the rising threat of antibiotic resistance should focus on implementing AMS programs in pharmacies and hospitals in Tanzania.

Prevalence of Extended-Spectrum β-Lactamase-Production among Clinical Gram-Negative Bacilli Isolates in A Tertiary Hospital, Southwest Nigeria

Extended spectrum β-lactamases (ESBLs) have emerged as important mechanisms of antimicrobial resistance to beta-lactam drugs in hospitals, thereby limiting the available treatment options for infections caused by these microorganisms. The objectives of this study were to determine the prevalence of ESBL production among clinical isolates of Gram-negative bacilli from Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria as part of the global efforts to provide information for the containment of the spread of antimicrobial resistance. This is a laboratory-based study of 186 consecutive non-duplicate Gram-negative bacilli (GNB) isolated from diverse clinical samples at the Microbiology laboratory of the hospital after standard aerobic cultures. The isolates were identified by conventional biochemical test scheme and commercial GNB API 20E identification kit. Antimicrobial susceptibility testing (AST) of each isolate was determined by the disk diffusion technique. Isolates presumptively identified as ESBL producers from the AST assay were confirmed by the combination disks method. Escherichia coli (n=43; 23.1%) predominated among the organisms, followed by Enterobacter spp (n=23; 12.4%) and Klebsiella spp (n=22; 11.8%). Most of the organisms (95.7%) were resistant to tetracycline and ampicillin, but the least resistance (4.3%) was exhibited to imipenem. Fifty-eight (31.2%) isolates were ESBL producers with a preponderance of E. coli (n=15; 25.9%). The ESBL producers were commonly isolated from urine samples (n=31; 53.4%), and were significantly more resistant to levofloxacin, ciprofloxacin, nalidixic acid, gentamicin, augmentin, cefepime, ceftriaxone, ceftazidime and cefotaxime (p<0.05). This study has highlighted the therapeutic implications of the presence of EBSL in clinical isolates which was depicted by their multi-drug resistance phenotypes, thus emphasizing the need for continuous surveillance of bacterial resistance, institution of antimicrobial resistance stewardship in our hospital and regular screening of ESBLs in clinical isolates to prevent treatment failure.

Antimicrobial Resistance Profiles and Genes in Streptococcus uberis Associated With Bovine Mastitis in Thailand.

Streptococcus uberis is recognized as an environmental mastitis pathogen in dairy cattle. The varied success rate of antibiotic treatment for S. uberis intramammary infection may be associated with the antimicrobial resistance (AMR) of these bacteria. This observational study aimed to analyze 228 S. uberis strains associated with bovine mastitis in northern Thailand from 2010 to 2017. AMR and AMR genes were determined by the minimum inhibitory concentration (MIC) using a microdilution method and polymerase chain reaction, respectively. The majority of S. uberis strains were resistant to tetracycline (187/228, 82.02%), followed by ceftiofur (44/228, 19.30%), and erythromycin (19/228, 8.33%). The MIC50 and MIC90 of ceftiofur in 2017 were 2–4-fold higher than those in 2010 (P < 0.01). Resistance to tetracycline and ceftiofur significantly increased between 2010 and 2017 (P < 0.05). The most common gene detected in S. uberis was tetM (199/228, 87.28%), followed by ermB (151/228, 66.23 %) and blaZ (15/228, 6.58 %). The association between tetracycline resistance and tetM detection was statistically significant (P < 0.01). The detection rates of tetM significantly increased, while the detection rates of tetO and ermB significantly decreased during 2010–2017. AMR monitoring for bovine mastitis pathogens, especially S. uberis, is necessary to understand the trend of AMR among mastitis pathogens, which can help create an AMR stewardship program for dairy farms in Thailand.

Treatment of Impetigo and Antimicrobial Resistance.

Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795.

Molecular characterization and antimicrobial resistance of potentially human\u2010pathogenic Escherichia coli strains isolated from riding horses

BackgroundTransmission of antimicrobial resistant and virulent Escherichia coli (E. coli) from animal to human has been considered as a public health concern. This study aimed to determine the phylogenetic background and prevalence of diarrheagenic E. coli and antimicrobial resistance in healthy riding-horses in Iran. In this research, the genes related to six main pathotypes of E. coli were screened. Also, genotypic and phenotypic antimicrobial resistance against commonly used antibiotics were studied, then phylo-grouping was performed on all the isolates.ResultsOut of 65 analyzed isolates, 29.23 % (n = 19) were determined as STEC and 6.15 % (n = 4) as potential EPEC. The most prevalent antimicrobial resistance phenotypes were against amoxicillin/clavulanic acid (46.2 %) and ceftriaxone (38.5 %). blaTEM was the most detected resistance gene (98.4 %) among the isolates and 26.15 % of the E. coli isolates were determined as multi-drug resistant (MDR). Three phylo-types including B1 (76.92 %), A (13.85 %) and D (3.08 %) were detected among the isolates.ConclusionsDue to the close interaction of horses and humans, these findings would place emphasis on the pathogenic and zoonotic potential of the equine strains and may help to design antimicrobial resistance stewardship programs to control the dissemination of virulent and multi-drug resistant E. coli strains in the community.

The Governance and Implementation of the National Action Plan on Antimicrobial Resistance in Tanzania: A Qualitative Study.

Tanzania launched its first National Action Plan (NAP) on antimicrobial resistance (AMR) in 2017 to reduce the burden of AMR in the country and contribute to the global response. We aimed to analyze the implementation of the NAP on AMR in Tanzania using the governance framework. In-depth interviews were conducted with human and animal health practitioners and national-level policy actors. We adapted Chua’s AMR governance framework to analyze the development and implementation of the NAP in Tanzania. Implementation of the NAP has realized several achievements, including: (i) the establishment of a functioning Multi-Sectoral Coordinating Committee for coordinating the implementation of AMR activities; (ii) existence of governance structure; (iii) establishment of human and animal surveillance sites; (iv) creation of AMR awareness in the community and (v) availability of guidelines at the health facility level to ensure AMR stewardship. However, some dimensions of the governance areas, including reporting and feedback mechanisms, accountability, transparency and sustainability of AMR plans, are not effectively implemented. Addressing these challenges should involve strengthening the collaboration of the different sectors involved at different NAP implementation levels by careful planning and coordination, and provision of adequate resources to ensure sustainability.

Treatment of Impetigo and Antimicrobial Resistance

Background: Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. Objectives: The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. Methods: The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. Results: The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. Conclusions: While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795

PIN142 High Cost of Treatment with NOVEL Antibiotics Compared to Standard of Care in Two EU Markets: Time for Subscription-Based Pricing?

Many novel antibiotics are intended to be effective against pathogens resistant to Standard of Care (SoC) antibiotics and attenuate progress of antimicrobial resistance. This study investigates the cost of novel antibiotics in UK and Germany compared to generic SoC and discusses opportunities that may remove barriers to use and offer increased value. Approved systemic IV and oral antibiotics (01/2010 – 06/2020) were extracted from the EMA website and pricing databases were reviewed to identify respective ex-manufacturer list prices in the UK and Germany. Antibiotics not commercially available/without publicly available pricing were excluded. Qualitative semi-structured interviews (n=10) were conducted with UK and Germany key clinical stakeholders to review the impact of price on utilization. Data for 9 novel antibiotics were analysed. 3 were approved for use in gram-negative infections, 5 in gram-positive, and 1 in gram-positive/negative. Cost of treatment with novel antibiotics (drug cost) compared to SoC antibiotics was on average 5X higher (range 1.4X – 16.2X). All novel antibiotics listed were restricted to 2nd or 3rd line use (once causative pathogen has been suspected/established). Respondents noted that cost is one of the key reasons novel antibiotics are restricted to 2nd or 3rd line use. In addition, they noted that the real-life value of novel antibiotics compared to SoC is more difficult to establish whilst their use is restricted to patients who have failed several therapies, often with complicated infections. As clinical experience increases, using these therapies in earlier lines where their comparative effectiveness against resistant pathogens can be better evaluated - as well as their benefit towards antimicrobial resistance stewardship - would help to demonstrate value. A subscription-based pricing structure may be one option to facilitate this.

COVID-19: Clouds Over the Antimicrobial Resistance Landscape

In recent years, the increase in antimicrobial resistance (AMR) has been recognized as a real threat to human and animal health. It is a problem that has been given the highest priority, uniting nations in the fight against its causes and effects. Among the actions that have been implemented are: clinical and microbiological surveillance, promotion of rational and controlled use of antibiotics, AMR stewardship programs in hospitals, development of tools for rapid diagnosis of infectious diseases to establish prompt and adequate treatment, and radically improving vaccination strategies. The current COVID-19 pandemic has placed disproportionate demands on the healthcare infrastructure and economy worldwide, which will negatively impact on the availability of materials as well as the technical capacity for diagnosis, patient care, and treatment of both COVID-19 and non-COVID-19 patients. Disruptions to production and distribution chains will hamper the availability and usage of antibiotics, also interrupting several of the activities that have been implemented thus far to combat AMR, including detailed laboratory monitoring and reinforced vaccination programs. Here, we discuss the main aspects that should be considered with regard to AMR, that may be affected by the pandemic and propose some actions to counter them.

Assessment of knowledge and attitude trends towards antimicrobial resistance (AMR) among the community members, pharmacists/pharmacy owners and physicians in district Sialkot, Pakistan

BackgroundAntimicrobial resistance (AMR) is an emerging threat to public health worldwide. A significant evidence has suggested that the knowledge and attitude trends among the community, pharmacists and physicians can play a critical role in managing the ever increasing threat of AMR.MethodsA cross-sectional survey was performed using three specific self-administered questionnaires for community members, pharmacists/pharmacy owners and physicians on a randomly selected sample population of 473, 424 and 308 respectively. Bivariate and multivariate logistic regression and Pearson chi-square tests were performed during data analysis.ResultA response rate of 81.2% (n = 385), 37.7% (n = 160) and 53.9% (n = 166) was achieved for general community, pharmacists/pharmacy owners and physicians respectively. More than half of the community participants (55.6%; n = 214) possess poor knowledge of AMR. Furthermore, knowledge and attitude of the community participants were also found to be significantly correlated (r2 = 0.02) with each other. In 90.6% (n = 145) of the pharmacies included in the survey, a qualified pharmacist was not present at the time of the operations. Only 36.9% physicians (n = 60) knew about the environmental route of dissemination of AMR. Majority of the physicians agreed that AMR is a global problem and also recognize the need for initiating AMR stewardship programs.ConclusionOur study will provide effective assessment and potential insights in designing tri-faceted interventions for rationalizing antibiotics consumption thus controlling the development and dissemination of AMR.

Effect of the duration of antimicrobial exposure on the development of antimicrobial resistance (AMR) for macrolide antibiotics: protocol for a systematic review with a network meta-analysis

BackgroundAntimicrobial resistance generates a huge health and economic burden and has the potential to become the leading cause of death globally, but its underlying drivers are yet to be fully described. The association between a microbe’s exposure to antimicrobials and subsequent development of, or selection for, resistance is well documented, as are the exacerbating microbial and human factors. However, the nature and extent of this risk, and how it varies by antimicrobial class and duration of treatment, is poorly defined. The goal of our systematic review and network meta-analysis is to determine the relationship between the duration of antimicrobial exposure and selection for resistance. We will use macrolides as the antimicrobial class of interest and Streptococcus pneumoniae carriage as an indicator organism. Our secondary outcomes include duration of symptoms, risk of treatment failure and recurrence, and descriptions of resistance mechanisms.MethodsWe will conduct a systematic review, selecting studies if they are published randomised controlled trials (RCTs) which report the relationship between taking a macrolide for any indication and incidence of resistant Streptococcus pneumoniae in patients of any age group. We will use a predefined search strategy to identify studies meeting these eligibility criteria in MEDLINE, Embase, Global Health and the Cochrane Central Register of RCTs. Two authors will independently screen titles and abstracts, review the full texts and undertake data extraction. We will use the Cochrane Collaboration’s tool to assess the quality of included RCTs. If feasible, we will perform pair-wise meta-analysis modelling to determine the relationship between the duration of macrolide treatment and development of macrolide resistant Streptococcus pneumoniae. If the identified studies meet the assumptions for a network meta-analysis (NMA), we will additionally model this relationship using indirect comparisons. Our protocol utilises reporting guidance by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the extensions for protocols (PRISMA-P) and network meta-analyses (PRISMA for NMA). Our review will also report to these standards.DiscussionEstablishing the relationship between the duration of antimicrobial exposure and development of, or selection for, resistance will inform the design of antimicrobial prescriptions, treatment guidelines and the behaviour of both physicians and patients. This work will therefore be a strong contribution towards the full realisation of current antimicrobial resistance stewardship strategies.Systematic review registrationPROSPERO CRD42018089275

Stewarding antibiotic stewardship in intensive care units with Bayesian artificial intelligence

Emerging antimicrobial resistance (AMR) is a global threat to life. Injudicious use of antibiotics is the biggest driver of resistance evolution, creating selection pressures on micro-organisms. Intensive care units (ICUs) are the strongest contributors to this pressure, owing to high infection and antibiotic usage rates. Antimicrobial stewardship programs aim to control antibiotic use; however, these are mostly limited to descriptive statistics. Genomic analyses lie at the other extreme of the value-spectrum, and together these factors predispose to siloing of knowledge arising from AMR stewardship. In this study, we bridged the value-gap at a Pediatric ICU by creating Bayesian network (BN) artificial intelligence models with potential impacts on antibiotic stewardship. Methods, actionable insights and an interactive dashboard for BN analysis upon data observed over 3 years at the PICU are described. BNs have several desirable properties for reasoning from data, including interpretability, expert knowledge injection and quantitative inference. Our pipeline leverages best practices of enforcing statistical rigor through bootstrapping, ensemble averaging and Monte Carlo simulations. Competing, shared and independent drug resistances were discovered through the presence of network motifs in BNs. Inferences guided by these visual models are also discussed, such as increasing the sensitivity testing for chloramphenicol as a potential mechanism of avoiding ertapenem overuse in the PICU. Organism, tissue and temporal influences on drug co-resistances are also discussed. While the model represents inferences that are tailored to the site, BNs are excellent tools for building upon pre-learnt structures, hence the model and inferences were wrapped into an interactive dashboard not only deployed at the site, but also made openly available to the community via GitHub. Shared repositories of such models could be a viable alternative to raw-data sharing and could promote partnering, learning across sites and charting a joint course for antimicrobial stewardship programs in the race against AMR.