Perspectives in the treatment of antibiotic-resistant bacterial infections with active photodynamic partners within the framework of the EURESTOP COST Action (CA21145).

The European Network for diagnosis and treatment of antibiotic-resistant bacterial infections-EURESTOP COST Action CA21145 focuses on tackling the burden of antimicrobial resistance (AMR) and has gathered many members working on photodynamic approaches. This European consortium is presented here in the One Health context, to highlight the potential of antimicrobial photodynamic therapy (aPDT) in the fight against AMR.

Strategies to reduce antimicrobials in livestock and aquaculture, and their impact under field conditions: a structured scoping literature review.

Antimicrobial resistance is a pandemic problem, causing substantial health and economic burdens. Antimicrobials are extensively used in livestock and aquaculture, exacerbating this global threat. Fostering the prudent use of antimicrobials will safeguard animal and human health. A lack of knowledge about alternatives to replace antimicrobials, and their effectiveness under field conditions, hampers changes in farming practices. This work aimed to understand the impact of strategies to reduce antimicrobial usage (AMU) in livestock and aquaculture, under field conditions, using a structured scoping literature review. The Extension for Scoping Reviews of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA-ScR) were followed and the Patient, Intervention, Comparison, Outcome, Time and Setting (PICOTS) framework used. Articles were identified from CAB Abstracts, MEDLINE and Scopus. A total of 7505 unique research articles were identified, 926 of which were eligible for full-text assessment; 203 articles were included in data extraction. Given heterogeneity across articles in the way alternatives to antimicrobials or interventions against their usage were described, there was a need to standardize these by grouping them in categories. There were differences in the impacts of the strategies between and within species; this highlights the absence of a 'one-size-fits-all' solution. Nevertheless, some options seem more promising than others, as their impacts were consistently equivalent or positive when compared with animal performance using antimicrobials. This was particularly the case for bioactive protein and peptides, and feed/water management. The outcomes of this work provide data to inform cost-effectiveness assessments of strategies to reduce AMU.

Estimating the Treatment and Prophylactic Economic Value of New Antimicrobials in Managing Antibiotic Resistance and Serious Infections for Common Pathogens in the USA: A Population Modelling Study.

BACKGROUND: Antimicrobial resistance is a growing public health concern. There is a global need to estimate the population-level value of developing new antimicrobials and to ensure the effective use of existing antimicrobials as strategies to counteract antimicrobial resistance. To this aim, population-level value criteria need to be considered alongside conventional value measures. OBJECTIVE: The objective of this study was to develop a novel modelling approach to estimate the value of new antimicrobials, considering the transmission, diversity and enablement elements of STEDI value. METHODS: We developed a population-based mathematical model for the assessment of antimicrobial value considering both prophylactic use of antimicrobials and the treatment of selected serious hospital-acquired infections in hospitals in the USA at a population level. Large-scale clinical and population healthcare data were used to inform a modelling-based analysis assessing the impact of introducing a new antimicrobial compared with continuing with no new antimicrobial, accounting for the transmission, diversity and enablement value of antimicrobial agents. RESULTS: Over a 10-year period, the addition of a new antimicrobial as part of an antimicrobial stewardship strategy in the USA was estimated to result in a proportional reduction of 9.03% in projected antimicrobial resistance levels. This yielded an estimated reduction of $64.3 million in hospitalization costs and a gain of over 153,000 quality-adjusted life-years at an economic value of over $15.4 billion over 10 years. Considering input uncertainty, the estimate of monetary benefit ranged from $11.1 to $21.4 billion. CONCLUSIONS: The use of a new antimicrobial for treatment and prophylactic indications yields considerable clinical and economic benefits including transmission diversity and enablement value. These findings may provide decision makers with important evidence to support investment in new antimicrobials and antimicrobial stewardship policy that address the patient, population and system burden associated with antimicrobial resistance.

Audit of antimicrobial stewardship in medical inpatients in Waikato, New Zealand 2021.

AIMS: Given the threat of rising antimicrobial resistance (AMR), 10 audit standards were selected to audit antimicrobial stewardship (AMS) in secondary care to assess guideline adherence and establish quality improvement initiatives in antimicrobial prescribing. METHODS: Patients were included if they received intravenous (IV) antibiotics across seven medical wards in Waikato or Thames hospitals, New Zealand, in November 2021. Audit standards were defined from the regional antimicrobial prescribing policy and adult antimicrobial guidelines. RESULTS: In total, 205 patients were audited. Microbiological sampling standards were met in 87 of 126 occasions (69.0%). Antimicrobial choices adhered to guidelines in 89 of 163 patients (54.6%), where guidelines were available. Documentation of antimicrobial indications in the medical notes and antimicrobial review at 48 to 72 hours met the standards at over 90%. Only 2 of 13 patients (15.4%) receiving piperacillin/tazobactam or a carbapenem were discussed with Infectious Diseases (ID). Documentation of indications and durations on paper-based medication charts was infrequent, around 12%. Evaluating for health equity, similar results were observed for Maori and non-Maori. CONCLUSIONS: Our audit identified specific areas for AMS quality improvement initiatives. Regular audit should become an essential element of the New Zealand AMS strategy. We believe increased AMS resources are required.

Validation, visibility, vagueness and variation: A qualitative assessment of existing veterinary guidelines for antimicrobial use in cattle and sheep in the UK.

Antimicrobials are essential in veterinary medicine to treat and control bacterial disease in animals. Their prudent use in food-producing animals has been encouraged to reduce the development and spread of antimicrobial resistance. National and international guidelines for responsible antimicrobial use have been developed as tools to guide and rationalise antimicrobial prescribing decisions by veterinarians and usage decisions by farmers. Yet, there is little understanding of whether these existing guidelines are fit for purpose. Accordingly, this study rigorously assessed 128 veterinary guidelines for antimicrobial use in ruminants in the UK, following established qualitative methodologies. Findings revealed four pertinent themes: validation of the veterinarian as the prescriber, visibility of responsible use realities, vagueness in interpretation and variation in directing behaviour. These themes encompassed the roles and responsibilities of the veterinarian and the realities of prescribing scenarios, alongside concerns relating to the specificity within and variation between guidelines. Resultant recommendations to inform and support the future development of guidelines include establishing species-specific and disease-specific guidelines, expanding guidelines to include disease prevention measures, including definitions to resolve vagueness and promoting congruence in interpretation, encouraging the development of practice-level guidelines to endorse collaboration and ownership, and fostering active working between stakeholders to align priorities and messaging.

Consideration of factors associated with inequalities in interventions that support health-care professionals' interaction with patients to reduce inappropriate antimicrobial use: a systematic review.

BACKGROUND: Tackling the public health challenge of antimicrobial resistance (AMR) requires promotion of appropriate antimicrobial use by health-care professionals. The objective of this review was to identify interventions that facilitate appropriate antimicrobial behaviours when health-care professionals interact with patients and any considerations for factors associated with health inequalities. METHODS: For this systematic review, we searched electronic databases (MEDLINE, EMBASE, Web of Science and Google Scholar) from Jan 31, 2023, to Feb 8, 2023. We included search terms such as antimicrobial use/prescribing, health-care professionals, and AMR programmes. We included any relevant primary study published from year 2010 and in English. We conducted forward and backward citation searching from included studies on March 27, 2023. We extracted information on the interventions following the Template for Intervention Description and Replication (TIDieR) guideline and examined reports on how the interventions might impact on inequalities. We performed quality assessment using the Mixed Methods Appraisal Tool (MMAT). We conducted descriptive synthesis. The protocol is registered with PROSPERO (CRD42023395642). FINDINGS: After screening 4979 records, we included 59 studies. Most studies were randomised trials (n=25) and qualitative/mixed methods studies (n=16). Included studies covered 16 countries, particularly the UK (n=16) and the USA (n=13). Most studies (n=34) fulfilled at least 80% of the relevant quality criteria, but 12 studies fulfilled less than 50%. Many interventions were established strategies (eg, TARGET: Treat Antibiotics Responsibly, Guidance, Education and Tools). Patient interaction elements of the interventions often involved using education materials (eg, digital/paper leaflets, and videos) and point-of-care testing. While many studies (n=49) included participants from disadvantaged groups, only three examined how outcomes differ between groups. In those studies, antimicrobial prescription was not associated with age, sex, and level of learning disability. Some other studies reported issues with language barriers and potential digital exclusion, especially for older people. INTERPRETATION: We might have missed some relevant studies due to publication year and language restrictions. Notwithstanding, this review showed that the potential impact of factors associated with health inequalities are not routinely considered during the implementation and evaluation of interventions to improve health-care professionals' interaction with patients. Future work should routinely consider this to help mitigate potential inequalities. FUNDING: UK Health Security Agency.

Value assessment of antimicrobials using the STEDI framework - How steady is the outcome?

Antimicrobial resistance (AMR) is one of the major threats to global population health, and the antimicrobial market requires substantial reimbursement reform and/or significant financial incentives to function properly. To address these challenges, England piloted a new health technology evaluation process in conjunction with a new payment model in 2019. The value assessment was performed using a dedicated broader value framework for antibiotics for the first time. This so-called STEDI framework is an acronym based on the five value elements it covers (Spectrum, Transmission, Enablement, Diversity, and Insurance value). Learnings from the pilot show that there are important considerations when implementing this value framework: The STEDI value profile of an antibiotic strongly depends on the local context and is impacted by trade-offs between individual value elements. Decision makers should therefore act carefully when applying STEDI to avoid distorting the overall evaluation result. Considering the STEDI value profile of an antibiotic is an important part of its value assessment as it allows for distinguishing between higher- and lower-value products. However, given the complexities surrounding its value assessment, further research must be undertaken to improve the overall STEDI evaluation process.

Variation in partial direct costs of treating clinical mastitis among 37 Wisconsin dairy farms.

The objective of this observational study was to describe variations in partial direct costs of clinical mastitis (CM) treatments among 37 dairy herds using data obtained from herd management records. Animal health and drug purchase records were retrospectively collected from 37 Wisconsin dairy herds for a period of 1 yr. Each farm was visited to verify case definitions, recording accuracy, and detection criteria of CM cases. Descriptive statistics were used to summarize cost of drugs and milk discard. Differences in costs among protocols, intramammary (IMM) products, parities, days in milk, and recurrence were analyzed using ANOVA. Of 20,625 cases of CM, 31% did not receive antimicrobial treatment. The average cost of drugs and milk discard (including cases that were not treated) was $192.36 ± 8.90 (mean ± SE) per case and ranged among farms from $118.13 to $337.25. For CM cases treated only with IMM antimicrobials, milk discard accounted for 87% of total costs and was highly influenced by duration of therapy. Differences in costs were observed among parities, recurrence, and stage of lactation at case detection. Eight different treatment protocols were observed, but 64% of cases were treated using only IMM antimicrobials. Treatment costs varied among protocols; however, cases treated using both IMM and injectable antimicrobials as well as supportive therapy had the greatest costs as they were also treated for the longest duration. Ceftiofur was used for 82% of cases that received IMM antimicrobials while ampicillin was used for 51% of cases treated using injectable antimicrobials. With the exception of ceftiofur and pirlimycin IMM products, many IMM products were given for durations that exceeded the maximum labeled duration. For cases treated using only IMM therapy, as compared with observed costs, we estimated that partial direct costs could be reduced by $65.20 per case if the minimum labeled durations were used. Overall, partial direct costs per case varied among herds, cow factors, and treatment protocols and were highly influenced by the duration of therapy.

Assessment of the quality of antimicrobial prescribing among hospitalized patients in a teaching hospital in Ghana: findings and implications.

OBJECTIVE: There is a need to assess the quality of antimicrobial prescribing in hospitals as a first step toward improving future prescribing to reduce antimicrobial resistance (AMR). This is in line with Ghana's National Action Plan. METHODS: A point prevalence survey of antimicrobial use was undertaken at the adult medical, surgical, and pediatric wards of Tamale Teaching Hospital using the standardized Global Point Prevalence Survey (GPPS) tool. Key target areas include adherence to current guidelines, limiting the prescribing of 'Watch' antibiotics with their greater resistance potential, and limiting the prescribing of antibiotics post-operatively to prevent surgical site infections (SSIs). RESULTS: Out of 217 patients' medical records assessed, 155 (71.4%) patients were prescribed antimicrobials. The rates were similar among children (73.9%) and adults (70.3%). Most of the antibiotics prescribed were in the WHO 'Watch' group (71.0%) followed by those in the 'Access' group (29%). Out of the 23 cases indicated for surgical antimicrobial prophylaxis to prevent SSIs, the majority (69.6%) were given doses for more than 1 day, with none receiving a single dose. This needs addressing to reduce AMR and costs. Guideline compliance with the current Ghanaian Standard Treatment Guidelines (GSTG) for managing infections was also low (28.7%). The type of indication was the only independent predictor of guideline compliance (aOR = 0.013 CI 0.001-0.127, p-value = 0.001). CONCLUSION: Given current concerns with antimicrobial prescribing in this hospital, deliberate efforts must be made to improve the appropriateness of prescribing to reduce AMR via targeted antimicrobial stewardship programs.

Applicability and limitations of quality indicator-based assessment of appropriateness in antimicrobial use: a comparison with expert opinion.

BACKGROUND: The effective implementation of antimicrobial stewardship requires an a-priori assessment of the appropriateness of antimicrobial prescriptions. AIM: To evaluate the effectiveness of quality indicators (QIs) in determining the appropriateness of antimicrobial prescriptions compared to that of expert opinions. METHODS: The study assessed antimicrobial use in 20 hospitals in Korea, with infectious disease specialists rating the appropriateness based on QIs and expert opinions. The selected QIs were (1) taking two blood cultures, (2) taking cultures from suspected sites of infection, (3) prescribing empirical antimicrobials according to guidelines, and (4) changing from empirical to pathogen-directed therapy for hospitalized patients and (2, 3, and 4) for ambulatory patients. Applicability, compliance with QIs, and agreement between QIs and expert opinions were investigated. FINDINGS: Overall, 7999 therapeutic uses of antimicrobials were investigated at the study hospitals. The experts rated 20.5% (1636/7999) as inappropriate use. For hospitalized patients, antimicrobial use was assessed based on all four QIs in 28.8% (1798/6234) of the cases. For ambulatory care patients, only 7.5% (102/1351) of the antimicrobial use cases were assessed using all three QIs. The agreement between expert opinions and all four QIs for hospitalized patients was minimal (κ = 0.332), whereas that between expert opinions and all three QIs for ambulatory patients was weak (κ = 0.598). CONCLUSION: QIs have limitations in determining the appropriateness of antimicrobial use, and the degree of agreement with expert opinions was low. Therefore, these QI limitations should be considered when determining the appropriateness of antimicrobial use.

Trends of antimicrobial use through selected antimicrobial indicators in Spanish hospitals, 2012 to 2021.

BACKGROUND: Surveillance of antimicrobial consumption is an important component of control strategies to tackle antimicrobial resistance. AIM: To evaluate the consumption of antimicrobials using six indicators proposed by the European Center for Disease Prevention and Control. METHODS: Point prevalence survey data on antimicrobial use in Spanish hospitals throughout the period 2012-2021 were analysed. A descriptive analysis of each indicator by year was performed globally and by hospital size. A logistic regression model was used to identify significant time trends. FINDINGS: In all, 515,414 patients and 318,125 antimicrobials were included. The prevalence of antimicrobial use remained stable throughout the study period (45.7%; 95% confidence interval (CI): 45.6-45.8). Percentages of antimicrobials for systemic use and those administered parenterally showed a small and significant increasing trend (odds ratio (OR): 1.02; 95% CI: 1.01-1.02; and OR: 1.03; 95% CI: 1.02-1.03, respectively). Small improvements were found in the percentages of antimicrobials prescribed for medical prophylaxis and with the reason for use documented in patients' medical records (-0.6% and 4.2%, respectively). The percentage of surgical prophylaxis prescribed for more than 24 h shows a significant improvement, decreasing from 49.9% (95% CI: 48.6-51.3) in 2012 to 37.1% (95% CI: 35.7-38.5) in 2021. CONCLUSION: During the last decade, Spanish hospitals have had a stable but high prevalence of antimicrobial use. Little to no improvement has been made in most of the indicators analysed, except for a reduction in the prescription of surgical prophylaxis for more than 24 h.

Pharmacoeconomic and antimicrobial stewardship analysis in waste management: Beyond switching drug administration route.

BACKGROUND: The aim of this study was to evaluate the impact of switch therapy of antimicrobials on cost reduction (pharmacoeconomic analysis) and hospital waste generation by switching from intravenous to oral therapy. This is a cross-sectional, observational, and retrospective study. METHODS: Data from 2019, 2020, and 2021, provided by the clinical pharmacy service of a teaching hospital in the interior of Rio Grande do Sul, were analyzed. The variables analyzed were intravenous and oral antimicrobials, frequency, duration of use, and total treatment time according to the institutional protocols. An estimate of the amount of waste not generated from the change of administration route was calculated by weighing the kits using a precision balance in grams. RESULTS: During the analyzed period, 275 switch therapy of antimicrobials were performed, resulting in US$ 55,256.00 of savings. The main antimicrobial classes that underwent changes were cephalosporins (25.1%), penicillins (22.55%), and quinolones (17.45%). Changing from intravenous to oral therapy avoided the generation of 170,631 g of waste, including needles, syringes, infusion bags, equipment, reconstituted solution bottles, and medication. CONCLUSIONS: The change from intravenous to the oral route of antimicrobials is safe for the patient, economically effective, and significantly reduces waste generation.

Healthcare-associated Infections Drive Antimicrobial Prescribing in Pediatric Departments at Three Academic Hospitals in South Africa.

BACKGROUND: The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals. METHODS: This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site. RESULTS: Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI. CONCLUSIONS: The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level.

Economic evaluation of antimicrobial usage surveillance in livestock.

There is increased pressure by governments and industry to develop national surveillance programmes to evaluate antimicrobial usage (AMU) in animals. This article presents a methodological approach to cost-effectiveness analysis of such programmes. Seven objectives are proposed for AMU surveillance in animals: quantifying use, finding trends, detecting hotspots, identifying risk factors, encouraging research, evaluating the impact of policies and diseases, and demonstrating compliance with regulations. Achieving these objectives would assist in making decisions about potential interventions, help to generate trust, incentivise the reduction of AMU and decrease the risk of antimicrobial resistance. The cost-effectiveness of each objective can be found by dividing the cost of the programme by the performance indicators of the surveillance required to meet the objective concerned. The precision and accuracy of surveillance outputs are suggested here as useful performance indicators. Precision depends on the level of surveillance coverage (SC) and surveillance representativeness (SR). Accuracy is influenced by the quality of farm records and SR. The authors argue that there is an increase in marginal cost for each unit increase of SC, SR and data quality. This is caused by the increasing difficulty of recruiting farmers due to potential barriers such as staff capacity, capital availability, computing literacy and availability, and geographical differences, among other factors. A simulation model was conducted to test the approach, using the quantification of AMU as the primary objective, and to provide evidence of the application of the law of diminishing returns. Cost-effectiveness analysis can be used to support decisions on the level of coverage, representativeness and data quality required in such AMU programmes.

Les gouvernements tout comme le secteur de l'élevage exercent une pression croissante pour que des programmes nationaux de surveillance soient élaborés afin d'évaluer l'utilisation d'agents antimicrobiens (UAM) chez les animaux. Cet article présente une approche méthodologique permettant de réaliser l'analyse coût-efficacité de ces programmes. Sept objectifs sont proposés pour la surveillance de l'UAM chez les animaux : quantifier cette utilisation, relever les tendances, détecter les situations d'utilisation intensive, déceler les facteurs de risque, encourager la recherche, évaluer l'impact des politiques et des maladies et démontrer la conformité avec les réglementations. La réalisation de ces objectifs de surveillance permettra de prendre des décisions éclairées sur les interventions à mener, contribuera à mettre en place un climat de confiance, encouragera à réduire l'UAM et atténuera le risque d'apparition d'antibiorésistances. Le ratio coût-efficacité de chaque objectif peut être déterminé en divisant le coût du programme par les indicateurs de performance de la surveillance requise pour chacun des objectifs examinés. Les auteurs considèrent que la précision et l'exactitude des résultats de la surveillance sont des indicateurs de performance utiles à cet effet. La précision dépend du niveau de couverture de la surveillance (CS) et de sa représentativité (RS). L'exactitude est fonction de la qualité des registres d'élevage et de la RS. D'après les auteurs, chaque accroissement unitaire de la CS, de la RS et de la qualité des données donne lieu à une augmentation du coût marginal. Celle-ci s'explique par la difficulté croissante de recruter des éleveurs pour cette activité, en raison d'obstacles tels que le manque d'effectifs, la disponibilité de capitaux, le manque de compétences et d'équipements informatiques et les différences géographiques, entre autres facteurs potentiels. Un modèle de simulation a été mis en oeuvre pour tester cette approche à partir de l'objectif principal (la quantification de l'UAM), et pour apporter des éléments démontrant l'application de la loi des rendements décroissants dans ce domaine. L'analyse coût-efficacité peut être utilisée pour étayer les décisions concernant la couverture, la représentativité et la qualité des données requises pour les programmes de surveillance de l'UAM.

Los gobiernos y la industria vienen presionando cada vez más para la implantación de programas nacionales de vigilancia destinados a evaluar el uso de agentes antimicrobianos (UAM) en los animales. Los autores presentan una solución metodológica para analizar la relación costo-eficacia de tales programas. En primer lugar proponen un conjunto de siete objetivos que deben cumplirse al vigilar el UAM en los animales: cuantificar el uso, detectar tendencias, localizar áreas de "gran intensidad" de uso, determinar los factores de riesgo, alentar la investigación, evaluar la repercusión de las políticas y las enfermedades y comprobar la observancia de los reglamentos. El logro de estos objetivos ayudaría a decidir sobre posibles intervenciones y a generar confianza, supondría un incentivo para reducir el UAM y atenuaría el riesgo de que surgieran resistencias a estos productos. Para cada objetivo es posible determinar la relación costo-eficacia dividiendo el costo del programa por los indicadores de desempeño de la vigilancia requerida para cumplir el objetivo en cuestión. Los autores proponen utilizar la precisión y exactitud de los resultados de la vigilancia como útiles indicadores de desempeño. La precisión depende del nivel de cobertura y de representatividad de la vigilancia. En la exactitud, por su parte, influyen la calidad de los archivos de las explotaciones pecuarias y la representatividad de la vigilancia. Los autores postulan que cada aumento unitario de la cobertura y la representatividad de la vigilancia y de la calidad de los datos se acompaña de un aumento correspondiente del costo marginal. Ello se explica por la creciente dificultad que presenta la participación de ganaderos en el proceso, debida a su vez a posibles barreras en aspectos como la dotación de personal, el capital disponible, los conocimientos en informática y el acceso a ordenadores o las diferencias geográficas, entre otros factores. Para ensayar el método y probar que se aplica el principio de los rendimientos decrecientes, los autores emplearon un modelo de simulación, utilizando como principal objetivo la cuantificación del UAM. El análisis de la relación costo-eficacia puede ser utilizado como herramienta auxiliar para tomar decisiones sobre el nivel de cobertura, representatividad y calidad de los datos que se necesita en este tipo de programas de vigilancia del UAM.

Assessment of CD200R Activation in Combination with Doxycycline in a Model of Melioidosis.

Antimicrobial resistance continues to be a global issue. Pathogens, such as Burkholderia pseudomallei, have evolved mechanisms to efflux certain antibiotics and manipulate the host response. New treatment strategies are therefore required, such as a layered defense approach. Here, we demonstrate, using biosafety level 2 (BSL-2) and BSL-3 in vivo murine models, that combining the antibiotic doxycycline with an immunomodulatory drug that targets the CD200 axis is superior to antibiotic treatment in combination with an isotype control. CD200-Fc treatment alone significantly reduces bacterial burden in lung tissue in both the BSL-2 and BSL-3 models. When CD200-Fc treatment is combined with doxycycline to treat the acute BSL-3 model of melioidosis, there is a 50% increase in survival compared with relevant controls. This benefit is not due to increasing the area under the concentration-time curve (AUC) of the antibiotic, suggesting the immunomodulatory nature of CD200-Fc treatment is playing an important role by potentially controlling the overactive immune response seen with many lethal bacterial infections. IMPORTANCE Traditional treatments for infectious disease have focused on the use of antimicrobial compounds (e.g. antibiotics) that target the infecting organism. However, timely diagnosis and administration of antibiotics remain crucial to ensure efficacy of these treatments especially for the highly virulent biothreat organisms. The need for early antibiotic treatment, combined with the increasing emergence of antibiotic resistant bacteria, means that new therapeutic strategies are required for organisms that cause rapid, acute infections. Here, we show that a layered defense approach, where an immunomodulatory compound is combined with an antibiotic, is better than an antibiotic combined with a relevant isotype control following infection with the biothreat agent Burkholderia pseudomallei. This approach has the potential to be truly broad spectrum and since the strategy includes manipulation of the host response it's application could be used in the treatment of a wide range of diseases.

Assessment of home storage of antimicrobials and its predictors in Mecha demographic surveillance and field research center: a cross-sectional study.

BACKGROUND: Home storage of antimicrobials is a worldwide practice. Irrational storage and inappropriate use of antimicrobials should get special attention in low-income countries due to limited information, knowledge, and perceptions. This study was conducted to survey home storage of antimicrobials and assess its predictors in Mecha Demographic Surveillance and Field Research Center (MDSFRC), Amhara region, Ethiopia. METHODS: A cross-sectional survey was conducted on 868 households. Predeveloped structured questionnaire was used to collect data on sociodemographics, knowledge on antimicrobials and perception about home stored antimicrobials. Data was analyzed using SPSS version 20.0 to execute descriptive statistics, and run binary and multivariable binary logistic regression. P-value < 0.05 was considered significant at 95% confidence level. RESULTS: The total number of households included in this study were 865. Female respondents represent 62.6%. The mean age (±) of respondents was 36.2 (± 13.93) years. The mean family size (±) of the household was 5.1 (± 2.5). Nearly one-fifth (21.2%) of the households stored antimicrobials at home with a condition similar to any household material. Most commonly stored antimicrobials were: Amoxicillin (30.3%), Cotrimoxazole (13.5%), Metronidazole (12.0%), and Ampicillin (9.6%). The most common immediate source of home stored antimicrobials was discontinuation of therapy (70.7%) either from symptomatic improvement (48.1%) or missing doses (22.6%). Predictors of home storage of antimicrobials with corresponding p-value were: age (0.002), family size (0.001), education status (< 0.001), home distance from the nearby healthcare institution (0.004), counseling while obtaining antimicrobials (< 0.001), knowledge level on antimicrobials (< 0.001), and perception of home stored antimicrobials as a wisdom (0.001). CONCLUSION: Substantial proportion of households stored antimicrobials in a condition that may exert selection pressure. To reduce home storage of antimicrobials and its consequences, stakeholders should give due attention to predictors variables related to sociodemographics, level of knowledge on antimicrobials, perception of home storage as a wisdom, and counseling service.

Validation of the Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) quality assessment tool.

BACKGROUND: The Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) was developed to undertake streamlined quality audits of antifungal prescribing. The validity and reliability of such tools is not characterized. OBJECTIVES: To assess the validity and reliability of the AF-NAPS quality assessment tool. METHODS: Case vignettes describing antifungal prescribing were prepared. A steering group was assembled to determine gold-standard classifications for appropriateness and guideline compliance. Infectious diseases physicians, antimicrobial stewardship (AMS) and specialist pharmacists undertook a survey to classify appropriateness and guideline compliance of prescriptions utilizing the AF-NAPS tool. Validity was measured as accuracy, sensitivity and specificity compared with gold standard. Inter-rater reliability was measured using Fleiss' kappa statistics. Assessors' responses and comments were thematically analysed to determine reasons for incorrect classification. RESULTS: Twenty-eight clinicians assessed 59 antifungal prescriptions. Overall accuracy of appropriateness assessment was 77.0% (sensitivity 85.3%, specificity 68.0%). Highest accuracy was seen amongst specialist (81%) and AMS pharmacists (79%). Prescriptions with lowest accuracy were in the haematology setting (69%), use of echinocandins (73%), mould-active azoles (75%) and for prophylaxis (71%). Inter-rater reliability was fair overall (0.3906), with moderate reliability amongst specialist pharmacists (0.5304). Barriers to accurate classification were incorrect use of the appropriateness matrix, knowledge gaps and lack of guidelines for some indications. CONCLUSIONS: The AF-NAPS is a valid tool, assisting assessors to correctly classify appropriate prescriptions more accurately than inappropriate prescriptions. Specialist and AMS pharmacists had similar performance, providing confidence that both can undertake AF-NAPS audits to a high standard. Identified reasons for incorrect classification will be targeted in the online tool and educational materials.