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Surveillance of antimicrobial consumption (AMC) is essential to anticipate and inform policies and public health decisions to prevent and/or contain antimicrobial resistance (AMR). This manuscript shares the experience on AMC data collection in Latin American & Caribbean (LAC). The WHO GLASS-AMC methodology for AMC surveillance was used for data registration during the period 2019–2022. Focal points belonging to each country were contacted and trained for AMC source of information detection, managing registration tools, and data analysis. Thirteen countries were enrolled with significant heterogeneity in the AMC results (range 2.55–36.26 DID-AMC). This experience reflects the heterogeneity of realities in LAC countries; how each one of the nations selected the best sources to collect AMC data, which were the main problems in applying the WHO-AMC collection tool, and the approach that each country gave to the analysis of its data. Finally, some examples are provided on the use of AMC information in making the best decision-making related to AMR control policies at the national level.
Reuterin is a broad-spectrum antimicrobial substance produced by lactic acid bacteria, and most previous studies have reported that reuterin is only produced under anaerobic conditions. If there are lactic acid bacteria that also produce it under aerobic conditions, it could be applied to fermented foods. In this study, it was found that Lactobacillus coryniformis WBB05 showed optimal reuterin production (123 mM reuterin from 200 mM glycerol) when incubated aerobically at 20°C. Furthermore, the minimum inhibitory concentration (MIC) of reuterin was determined for starter lactic acid bacteria strains and cheese moulds. MIC toward Penicillium camemberti was 0.125 mM and the white mould starter was much more sensitive than other moulds.
The purpose of the research paper was firstly to identify bacteriocin-producing lactic acid bacteria characterizing strains with anti-listeria activity and, secondly, to characterize bacteriocin evaluating its in vitro efficiency as a natural preservative and, thirdly, to evaluate the anti-listeria effect of the bacteriocinogenic strain of Lactiplantibacillus plantarum in cheeses and produce an edible film with anti-listerial effect. Of 355 lactic acid bacteria strains tested, two were able to produce bacteriocin against Listeria monocytogenes and were identified as Lactiplantibacillus plantarum and Lactiplantibacillus pentosus. A bactericidal effect of strain QS494 (Lactiplantibacillus plantarum) was observed in the first 8 h, with a reduction of 1.7 log, using cell-free supernatant with Listeria monocytogenes, where viable cells were counted on listeria selective agar. Both strains showed good technological characteristics and were without production of virulence factors. Changes in the pH of the cell-free supernatant obtained from Lactiplantibacillus plantarum did not affect its antimicrobial activity, which remained stable after heat treatments for up to 15 min at 121°C. Inhibitory activity was also observed after 12 weeks of storage at −20°C. In the evaluation of the anti-listeria effect in cheeses, a 3 log reduction in the Listeria monocytogenes count was observed in 120 h in cheeses produced with bacteriocinogenic lactic acid bacteria, while in cheeses produced with non-bacteriocinogenic culture, we observed a 2 log increase in the count. Edible films produced with the addition of precipitate from the cell free supernatant showed an antimicrobial effect against Listeria monocytogenes. Thus, the two strains studied have technological and biosafety potential.
Several countries have shown an increased prevalence of drug resistance in animal production due to the indiscriminate use of antibiotics and antiparasitics in human and veterinary medicine. This article aims to review existing methods using naturally occurring essential oils (EOs) and their isolated compounds (EOCs) as alternatives to antimicrobials and antiparasitic compounds in animal production and, consequently, to avoid resistance. The most-reported mechanism of action of EOs and EOCs was cell membrane damage, which leads to the leakage of cytoplasmic content, increased membrane permeability, inhibition of metabolic and genetic pathways, morphologic changes, antibiofilm effects, and damage to the genetic material of infections. In parasites, anticoccidial effects, reduced motility, growth inhibition, and morphologic changes have been reported. Although these compounds regularly show a similar effect to those promoted by traditional drugs, the elucidation of their mechanisms of action is still scarce. The use of EOs and EOCs can also positively influence crucial parameters in animal production, such as body weight gain, feed conversion rate, and cholesterol reduction, which also positively impact meat quality. The application of EOs and EOCs is enhanced by their association with other natural compounds or even by the association with synthetic chemicals, which has been found to cause synergism in their antimicrobial effect. By reducing the effective therapeutical/prophylactic dose, the chances of off-flavors – the most common issue in EO and EOC application – is greatly mitigated. However, there is very little work on the combination of EOs and EOCs in large in vivo studies. In addition, research must apply the correct methodology to properly understand the observed effects; for example, the use of only high concentrations may mask potential results obtained at lower dosages. Such corrections will also allow the elucidation of finer mechanisms and promote better biotechnologic use of EOs and EOCs. This manuscript presents several information gaps to be filled before the use of EOs and EOCs are fully applicable in animal production.
This research paper aimed to evaluate the association between feeding waste milk to calves and the occurrence of antimicrobial multi-resistance by extended spectrum β-lactamase (ESBL) enzymes through determining their production by E. coli isolates from 32 dairy farms. Among β-lactamase enzymes, ESBL provide resistance to a wide variety of β-lactam antimicrobials including penicillin and 2nd, 3rd and 4th generation cephalosporins. Feeding waste milk to calves has been observed to lead to increased antimicrobial resistance in faecal isolates of calves. In each farm included in this study, faecal samples were collected from the rectum of five healthy calves in the first month of life and pooled into a single container. Five isolates from each pool were selected and confirmed to be E. coli by amplification of the 16S rRNA gene. ESBL production was confirmed phenotypically on 148 isolates from 31 farms by use of the double-disk synergy test. Genotypic confirmation of ESBL production was performed by PCR for the genes blaCTX-M-1, −2, −8, −9 and blaCMY-2. A questionnaire was also performed and a mixed logistic regression model was used to identify risk factors for the occurrence of antimicrobial resistance. A negative binomial regression model was also used, in order to assess whether there was any association between certain farm management practices and the number of ESBL-producing E. coli isolates from each farm. Phenotypic confirmation of ESBL production was obtained on 40 E. coli isolates from 15 farms (48.4%), whereas genotypic confirmation was obtained on 55 isolates from 20 farms (64.5%). The use of three or more different intramammary antimicrobials to treat mastitis within the previous year significantly impacted the number of ESBL-producing E. coli isolates; on farms that did so, there were more isolates in which ESBL-producing E. coli was present, when compared to farms that had used less formulations within the same time span.
Antagonism among bacteria is widespread and plays an important role in structuring communities. Inhibitory compounds can confer competitive advantage, but energetic trade-offs can result in non-transitive (i.e. ‘rock-paper-scissors’) interactions, ultimately allowing co-existence and community stability. Competition in sedimentary habitats is especially keen given high densities and attachment to inorganic particles. Because measuring trade-offs between bacterial species is challenging, much of our understanding of competitive interactions is based on theoretical modelling and simplified in vitro experiments. Our objectives were to determine (1) if interference competition occurs in microcosms mimicking in situ conditions; (2) whether the presence of sediment influences antagonistic interactions; and (3) if more complex assemblages alleviate or synergize interactions. Four sedimentary isolates, including antibiotic-producing, resistant and susceptible strains were incubated in porewater microcosms in 1-, 2- and 3-species combinations, both with and without natural sediments. Microcosms were sampled over 72 h to generate growth curves using quantitative PCR. Multiple growth attributes (growth rate, maximum density, lag time) were used to assess effects of treatment (species combinations) and environment (sediment vs porewater alone). Antimicrobial producers were more effective at inhibiting target species in microcosms that included sediment, in agreement with theory. We observed growth inhibition by antimicrobial-producing bacteria in both 2- and 3-species microcosms. However, the expected protection of sensitive bacterial strains by resistant strains was observed in only one (of four) 3-species combinations, thus the ‘rock-paper-scissors’ prediction was not fully supported. These results reinforce the notion that interspecies interactions are context-dependent, reliant on environmental conditions and the species involved.
Necrotising otitis externa is a severe ear infection for which there are no established diagnostic or treatment guidelines.
Method
This study described clinical characteristics, management and outcomes for patients managed as necrotising otitis externa cases at a UK tertiary referral centre.
Results
A total of 58 (63 per cent) patients were classified as definite necrotising otitis externa cases, 31 (34 per cent) as probable cases and 3 (3 per cent) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49–44.9 weeks). Six per cent of patients relapsed a median of 16.4 weeks (interquartile range, 23–121) after stopping antimicrobials. Twenty-eight per cent of cases had complex disease. These patients were older (p = 0.042), had a longer duration of symptoms prior to imaging (p < 0.0001) and higher C-reactive protein at diagnosis (p = 0.005). Despite longer courses of intravenous antimicrobials (23 vs 14 days; p = 0.032), complex cases were more likely to relapse (p = 0.016).
Conclusion
A standardised case-definition of necrotising otitis externa is needed to optimise diagnosis, management and research.
To assess the effect of individual compared to clinic-level feedback on guideline-concordant care for 3 acute respiratory tract infections (ARTIs) among family medicine clinicians caring for pediatric patients.
Design:
Cluster randomized controlled trial with a 22-month baseline, 26-month intervention period, and 12-month postintervention period.
Setting and participants:
In total, 26 family medicine practices (39 clinics) caring for pediatric patients in Virginia, North Carolina, and South Carolina were selected based upon performance on guideline-concordance for 3 ARTIs, stratified by practice size. These were randomly allocated to a control group (17 clinics in 13 practices) or to an intervention group (22 clinics in 13 practices).
Interventions:
All clinicians received an education session and baseline then monthly clinic-level rates for guideline-concordant antibiotic prescribing for ARTIs: upper respiratory tract infection (URI), acute bacterial sinusitis (ABS), and acute otitis media (AOM). For the intervention group only, individual clinician performance was provided.
Results:
Both intervention and control groups demonstrated improvement from baseline, but the intervention group had significantly greater improvement compared with the control group: URI (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.37–1.92; P < 0.01); ABS (OR, 1.45; 95% CI, 1.11–1.88; P < 0.01); and AOM (OR, 1.59; 95% CI, 1.24–2.03; P < 0.01). The intervention group also showed significantly greater reduction in broad-spectrum antibiotic prescribing percentage (BSAP%): odds ratio 0.80, 95% CI 0.74-0.87, P < 0.01. During the postintervention year, gains were maintained in the intervention group for each ARTI and for URI and AOM in the control group.
Conclusions:
Monthly individual peer feedback is superior to clinic-level only feedback in family medicine clinics for 3 pediatric ARTIs and for BSAP% reduction.
Trial registration:
ClinicalTrials.gov identifier: NCT04588376, Improving Antibiotic Prescribing for Pediatric Respiratory Infection by Family Physicians with Peer Comparison.
Our study was conducted to assess the sepsis-associated hospitalisations and antimicrobials prescribed for sepsis inpatients in Hong Kong. Demographic, diagnostic and antimicrobial prescription data were analysed for patients admitted to public hospitals with a diagnosis of septicaemia from 2000 to 2015. A total of 223 250 sepsis hospitalisations were recorded in Hong Kong from 2000 to 2015 during which the hospitalisation rate increased by 85.6%. The majority of the sepsis hospitalisations occurred in adults ≥65 years and children aged 0–4 years. Adults with a secondary diagnosis of sepsis were often admitted with a primary diagnosis of urological conditions or pneumonia; whereas diabetes mellitus was the most common secondary diagnosis among those with primary sepsis. Paediatric sepsis patients aged 0–4 years were often diagnosed with disorders relating to short gestation and low birthweight. Antimicrobial prescriptions increased by 51.1% and 34.4% for primary and secondary sepsis patients, respectively. β-Lactam and β-lactamase inhibitor combinations were the most used antibiotics whereas the usage of carbapenems increased more than 10 times over the study period. A substantial burden of hospitalisations was attributable to sepsis in Hong Kong, particularly in the extremes of age. Broad-spectrum and last-resort antibiotics had been increasingly dispensed for sepsis inpatients.
The aim was to determine the association between healthcare workers’ (HCWs) country of birth and their knowledge of appropriate use of antibiotics, and whether the association changed after an educational intervention.
Background:
Older residents in nursing homes have been recognized to receive excessively antibiotic treatments. HCWs often represent an important link between the older resident and the general practitioner prescribing the antibiotics, thus their knowledge of appropriate use of antibiotics is important.
Methods:
This study was conducted as a prospective pre-post study. Totally, 312 HCWs from 7 nursing homes in Denmark were included. For statistical analyses, χ2 test and a linear mixed regression model were applied.
Findings:
Native HCWs were more likely to have a higher percentage of correct responses to single statements related to knowledge of appropriate use of antibiotics. Native HCWs had a significantly higher knowledge-of-antibiotic score compared to foreign HCWs (−7.53, P < 0.01). This association remained significant after adjusting for relevant covariates (−5.64, P < 0.01). Native HCWs’ mean change in knowledge-of-antibiotic score after the intervention did not differ from the foreign HCWs’ mean change in knowledge-of-antibiotic score.
Conclusion:
Our findings indicate that HCWs born outside Denmark reveal a lower knowledge-of-antibiotic score than HCWs born in Denmark despite comparable educational backgrounds. All participants increased their knowledge from baseline to follow-up. Our findings also indicate that an educational seminar cannot equalize the difference in knowledge between native and foreign HCWs. Studies with larger sample size and a more detailed measurement of cultural identity should investigate this association further.
Mastitis, inflammation of the bovine mammary gland, is generally caused by intramammary infection with bacteria, and antimicrobials have long been a corner stone of mastitis control. As societal concern about antimicrobial use in animal agriculture grows, there is pressure to reduce antimicrobial use in dairy farming. Point-of-care tests for on-farm use are increasingly available as tools to support this. In this Research Reflection, we consider available culture-dependent and culture-independent tests in the context of ASSURED criteria for low-resource settings, including convenience criteria, scientific criteria and societal criteria that can be used to evaluate test performance. As tests become more sophisticated and sensitive, we may be generating more data than we need. Special attention is given to the relationship between test outcomes and treatment decisions, including issues of diagnostic refinement, antimicrobial susceptibility testing, and detection of viable organisms. In addition, we explore the role of technology, big data and people in improved performance and uptake of point-of-care tests, recognising that societal barriers may limit uptake of available or future tests. Finally, we propose that the 3Rs of reduction, refinement and replacement, which have been used in an animal welfare context for many years, could be applied to antimicrobial use for mastitis control on dairy farms.
This introduction outlines the scope of the book titled “Challenges in Tackling Antimicrobial Resistance: Economic and Policy Responses”, and then summarises the main messages of each chapter which focus on the following big questions around AMR policy. What is the evidence on the rise of AMR and its health and economic impact? How can it be most effectively addressed in the community and in hospitals? What role is played by antimicrobial use in the food and livestock sector and what can be done about it? How can the discovery of new antibiotics be reinvigorated to replace those rendered ineffective by resistance?What needs to be done to develop new diagnostic tests so that infections can be speedily identified or ruled out and unnecessary antibiotic use avoided? Can more use be made of vaccines to tackle AMR? How have civil society movements contributed to policy development in the fight against AMR? What does the international community need to do in terms of global collective action to tackle AMR?
Vaccination is one of the most effective measures to reduce antimicrobial resistance in both human and animal pathogens. There are multiple pathways by which vaccines may act to reduce resistance: theycan prevent infections by focal pathogens, reducing the need to use antibiotics; they can selectively protect against resistant subtypes of a pathogen; they can reduce infections by other pathogen species which are routinely treated with antibiotics (not necessarily appropriately) thus reducingbystander selection;and they could selectively reduce transmission in settings such as hospitals which may have higher proportions of resistant strains. Because vaccines are highly specific to their targeted pathogens, they are much less likely to induce resistance compared to antibiotics. Hence they can be delivered to large populations as a preventive measure to reduce transmission. The impact of vaccination on resistance has been demonstrated for vaccines against Streptococcus pneumoniae, Haemophilus influenzae type b and influenza. Current and pipeline vaccines against pathogens such as Vibrio cholerae, Escherichia coli, Salmonella typhi, RSV, diarrhoeal viruses and nosocomial bacteria may also have potential to reduce resistance. Economic evaluations of vaccines need to be expanded to capture their benefits in reducing resistance, in order to incentivize development and introduction of the right vaccines. Accurately doing so will require health systems, epidemiological and economic research.
Antimicrobial resistance (AMR) has profound consequences for the treatment of infections. By limiting treatment options, it often makes it necessary to resort to antibiotics with a broader spectrum of action some of which are potentially less effective or safe than narrow-spectrum antibiotics. This limitation in our ability to treat infections effectively has an impact on health care budgets but also broader and potentially disastrous consequences on a variety of economic sectors. This chapter provides an overview of the health and economic burden of AMR. It first presents the current state of knowledge on the epidemiology of AMR and discusses the main analytical challenges in determining the current and long-term effects of resistance on populations in terms of morbidity, mortality, and length of hospital stay. In addition, a summary of the current literature on the economic impact of AMR is provided along with a detailed discussion of the characteristics and limitations of existing economic models. Finally, it identifies the main knowledge gaps and suggests avenues for future research and approaches to address them.
An effective global AMR response will require diagnostics that are affordable and accessible, can be used at the point-of-care (POC), and can rapidly determine antimicrobial susceptibility or detect resistance. These tests are urgently needed to guide patient management, reduce inappropriate use of antibiotics and improve patient outcomes. POC tests with resistance detection and data transmission capabilities will be useful for AMR surveillance to monitor AMR trends and detect emergence of novel resistance in real time to enable timely optimisation of AMR strategies. Connected diagnostics have the potential to improve the efficiency of health care systems by simplifying patient pathways, guiding appropriate use of drugs and other resources and improving patient outcomes. POC tests are also useful in reducing the cost of R&D for new antibiotics. To ensure innovation in diagnostics development and deployment, a sound business case needs to be made to quantify the risk of not having diagnostics to improve the specificity of syndromic management. Financing mechanisms to incentivize diagnostic innovation, de-risk R&D and to finance the deployment of novel diagnostic solutions for AMR within different health systems are urgently needed.
Antimicrobial resistance (AMR) is a biological mechanism whereby a micro-organism evolves over time to develop the ability to become resistant to antimicrobial therapies such as antibiotics. The drivers of and potential solutions to AMR are complex, often spanning multiple sectors. The internationally recognised response to AMR advocates for a 'One Health' approach, which requires policies to be developed and implemented across human, animal, and environmental health. To date, misaligned economic incentives have slowed the development of novel antimicrobials and limited efforts to reduce antimicrobial usage. However, the research which underpins the variety of policy options to tackle AMR is rapidly evolving across multiple disciplines such as human medicine, veterinary medicine, agricultural sciences, epidemiology, economics, sociology and psychology. By bringing together in one place the latest evidence and analysing the different facets of the complex problem of tackling AMR, this book offers an accessible summary for policy-makers, academics and students on the big questions around AMR policy. This title is available as Open Access on Cambridge Core.
Leptospirosis is a worldwide zoonotic disease determined by pathogenic spirochetes of the genus Leptospira. The control of bovine leptospirosis involves several measures including antibiotic treatment of carriers. Despite its importance, few studies regarding antimicrobial susceptibility of strains from bovine origin have been conducted. The aim of this study was to determine the in vitro susceptibility of Leptospira strains obtained from cattle in Rio de Janeiro, Brazil, against the main antibiotics used in bovine veterinary practice. A total of 23 Leptospira spp. strains were investigated for minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) using broth macrodilution. At the species level, there were not differences in MIC susceptibility except for tetracycline (P < 0.05). Nevertheless, at the serogroup level, differences in MIC were observed among Sejroe strains, mainly for ceftiofur, doxycycline and in MBC for streptomycin (P < 0.05). One strain presented MBC values above maximum plasmatic concentration described for streptomycin and was classified as presenting reduced susceptibility. Efficacy of antimicrobial therapy on bovine leptospirosis could be compromised due to occurrence of infection by Leptospira strains presenting reduced susceptibility.
In dairy herds, application of antimicrobials at drying-off is a common mastitis control measure. This article describes a protocol for systematic review and meta-analysis to address three crucial points regarding antimicrobial usage at drying-off: (1) comparative efficacy of antimicrobials used for preventing new and eliminating existing intramammary infections (IMI); (2) comparison of selective and blanket dry cow therapy approaches in preventing new and eliminating existing IMI; and (3) assessment of the extra prevention against new IMI that can be gained from using antimicrobial-teat sealant combinations versus antimicrobials alone. Five PICO (Population, Intervention, Comparator, Outcome) questions were formulated to cover the three objectives of the review. Medline, CAB Abstracts, Web of Science, and conference proceedings will be searched along with iterative screening of references. Articles will be eligible if: (1) published after 1966; (2) written in English or French; and (3) reporting field clinical trials and observational studies, conducted on dairy cows at drying-off, with at least one antimicrobial-treated group and one IMI-related outcome. Authors will independently assess the relevance of titles and abstracts, extract data, and assess bias and the overall quality of evidence. Results will be synthesized and analyzed using pairwise and network meta-analysis. The proposed study will significantly update previously conducted reviews.
Royal Jelly (RJ) is product from bees that is used to feed larvae in the hive as well as a main nutritional source for the queen honey bee. It has various important biological activities including as an antioxidant, immunomodulatory, anti-inflammatory, antimicrobial, cholesterol-lowering, and growth promoter activities and has the ability for inhibition of certain enzymatic degradation. It can be used for the improvement of growth performance, gut health and quality and safety of animal products in poultry due to its antioxidant and immune modulating properties. The antioxidant activity of RJ is mainly due to the presence of polyphenolic compounds. It is an excellent source of B and C vitamins and folic acid. The mineral profile of RJ is useful as it contains major macro and micro minerals. Studies conducted on supplementation with RJ in poultry diets have shown a significant increase in body weight, egg production, and immune levels and is especially useful in organic production. Supplementation of RJ at the level of 10 and 15 mg/kg in layer diets positively influenced egg weight (by 5.0% and 4.8% respectively), egg production (10.5% and 11.0% respectively), weight gain of hens (7.0% and 6.5% respectively) and yolk pigmentation (9.5% and 9.7% respectively). Total leukocyte and erythrocyte counts in the diet containing 200 mg/kg RJ were significantly higher than the diet contained 100 mg/kg or the unsupplemented control group. However, the heterophil/lymphocyte ratio and heterophil percent were reduced in RJ-fed groups. Supplementing poultry diets with RJ offers an opportunity to maximise profit from safe and high quality poultry production.
There is increasing research interest in potential applications of halloysite as fillers for polymer composites, controlled drug delivery, carriers for the supply and sustained release of active agents for anticorrosion coatings, in nanoreactors or nanotemplates, and for the uptake of contaminants or pollutants and support for catalysts. In this review, recent findings in terms of the prospects and challenges of using halloysite nanotubes (HNTs) in different polymeric matrices targeting a range of old and new applications are discussed and evaluated. The compositions include chitosan/halloysite membranes as bone-tissue scaffolds, polylactic acid (PLA)/halloysite membranes for food-packaging applications and their antimicrobial activities, instrumented impact properties of epoxy/halloysite nanocomposites and the role of halloysite in the self-healing of epoxy composites, polyacryronitrile (PAN)/halloysite membranes for use in water filtration as well as a review of some recent applications of halloysite/alginate beads in the adsorption of contaminants such as lead.