Pub Date : 2023-12-07DOI: 10.3389/frabi.2023.1291046
Williams Walana, E. K. Vicar, E. Kuugbee, Francis Sakida, I. Yabasin, Eric Faakuu, Solomon Amfoabegyi, J. Ziem
Antimicrobial resistance (AMR) remains a significant health challenge globally and nations have the responsibility to maintain a constant surveillance of AMR, particularly for the emergence of multidrug-resistant (MDR) isolates to existing antibiotics. Against this backdrop, we applied the WHO’s AWaRe (ACCESS, WATCH, and RESERVE) antibiotics classification and the European Centre for Disease Prevention and Control (ECDC)’s multidrug resistance definition for AMR isolates from clinical specimens.This study reviewed bacterial culture and antibiotic sensitivity test outcomes. These results were then grouped according to the AWaRe and ECDC-MDR classifications.In all, the culture and sensitivity results of the 3,178 clinical specimens were investigated, of which 59.5% were from female patients. The pathogens were isolated from 1,187 specimens (37.4%). The WHO’s ACCESS antibiotics, tetracycline, showed a relatively high level of insusceptibility, particularly among Gram-positive (GP) isolates (ranging from 66.7% to 76.7%), along with augmentin (ranging from 44.7% to 81.3%) and cloxacillin (ranging from 50.0% to 78.1%). However, the Gram-negative (GN) isolates showed a relatively high level of susceptibility to amikacin, augmentin, and nitrofurantoin. The WHO’s WATCH antibiotics, cefuroxime, ceftriaxone, cefotaxime, and ciprofloxacin showed a relatively high level of non-responsiveness among the GN isolates, particularly Proteus (ranging from 31.4% to 78.4%), Pseudomonas (ranging from 21.4% to 96.4%), and Enterobacter (ranging from 62.5% to 100%) spp. Among the WHO’s RESERVE antibiotics, resistance to ceftazidime was commonly associated with the GN coliform isolates: Eschericha coli, Klebsiella, and Citrobacter spp. Insusceptibility to meropenem was frequently observed in Staphylococcus spp., E. coli, coliforms, and Proteus spp. Out of the 1,187 isolates, 15.5% (184) were GAT (gentamycin, ampicillin, and tetracycline) MDR, of which 61% (112/184) were from specimens of female patients. The most predominant GAT-MDR isolates were Staphylococcus spp., E. coli, coliforms, and Klebsiella spp.In conclusion, the study revealed a relatively high level and diverse range of AMR. However, MDR in accordance with the ECDC definition was relatively low. There is, therefore, a need to have further research on AMR to inform national criteria for MDR in Ghana.
{"title":"Antimicrobial resistance of clinical bacterial isolates according to the WHO’s AWaRe and the ECDC-MDR classifications: the pattern in Ghana’s Bono East Region","authors":"Williams Walana, E. K. Vicar, E. Kuugbee, Francis Sakida, I. Yabasin, Eric Faakuu, Solomon Amfoabegyi, J. Ziem","doi":"10.3389/frabi.2023.1291046","DOIUrl":"https://doi.org/10.3389/frabi.2023.1291046","url":null,"abstract":"Antimicrobial resistance (AMR) remains a significant health challenge globally and nations have the responsibility to maintain a constant surveillance of AMR, particularly for the emergence of multidrug-resistant (MDR) isolates to existing antibiotics. Against this backdrop, we applied the WHO’s AWaRe (ACCESS, WATCH, and RESERVE) antibiotics classification and the European Centre for Disease Prevention and Control (ECDC)’s multidrug resistance definition for AMR isolates from clinical specimens.This study reviewed bacterial culture and antibiotic sensitivity test outcomes. These results were then grouped according to the AWaRe and ECDC-MDR classifications.In all, the culture and sensitivity results of the 3,178 clinical specimens were investigated, of which 59.5% were from female patients. The pathogens were isolated from 1,187 specimens (37.4%). The WHO’s ACCESS antibiotics, tetracycline, showed a relatively high level of insusceptibility, particularly among Gram-positive (GP) isolates (ranging from 66.7% to 76.7%), along with augmentin (ranging from 44.7% to 81.3%) and cloxacillin (ranging from 50.0% to 78.1%). However, the Gram-negative (GN) isolates showed a relatively high level of susceptibility to amikacin, augmentin, and nitrofurantoin. The WHO’s WATCH antibiotics, cefuroxime, ceftriaxone, cefotaxime, and ciprofloxacin showed a relatively high level of non-responsiveness among the GN isolates, particularly Proteus (ranging from 31.4% to 78.4%), Pseudomonas (ranging from 21.4% to 96.4%), and Enterobacter (ranging from 62.5% to 100%) spp. Among the WHO’s RESERVE antibiotics, resistance to ceftazidime was commonly associated with the GN coliform isolates: Eschericha coli, Klebsiella, and Citrobacter spp. Insusceptibility to meropenem was frequently observed in Staphylococcus spp., E. coli, coliforms, and Proteus spp. Out of the 1,187 isolates, 15.5% (184) were GAT (gentamycin, ampicillin, and tetracycline) MDR, of which 61% (112/184) were from specimens of female patients. The most predominant GAT-MDR isolates were Staphylococcus spp., E. coli, coliforms, and Klebsiella spp.In conclusion, the study revealed a relatively high level and diverse range of AMR. However, MDR in accordance with the ECDC definition was relatively low. There is, therefore, a need to have further research on AMR to inform national criteria for MDR in Ghana.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"52 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138593243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-05DOI: 10.3389/frabi.2023.1276982
Ishrat Jabeen, Sohidul Islam, A. K. M. I. Hassan, Zerin Tasnim, Sabbir R Shuvo
Citrobacter spp. are Gram-negative, non-spore forming, rod-shaped, facultative anaerobic bacteria from the Enterobacteriaceae family often found in soil, sewage, sludge, water, food, and the intestinal tracts of animals and humans. Several members of Citrobacter spp. especially C. freundii, C. koseri, C. braakii are frequently detected in newborn illnesses, urinary tract infections, and patients with severe underlying conditions, including hypertension, diabetes, cancer, and respiratory infections, or those who are immunocompromised. Strains of Citrobacter spp. can spread vertically or horizontally from carriers or other hospital sources and thus cause nosocomial infections in hospital settings. A total of 19 Citrobacter genomospecies have been recognized based on genomics. It has been noted that the Citrobacter genus acquired antimicrobial resistance and virulence, including invasion, colonization, biofilm formation, and toxin production. The recent emergence and spread of antimicrobial resistance to β-lactams, carbapenems, fluoroquinolones, aminoglycosides, and colistin in Citrobacter spp. through chromosomal and plasmid-mediated resistance limits the empiric treatment options. Therefore, combination therapy involving costly and potentially hazardous antibiotics poses significant challenges in treating Citrobacter infections. Here we summarized the nomenclature of Citrobacter spp., clinical manifestations, epidemiology, pathogenesis, antibiotic resistance mechanisms, and treatments from various clinical samples. This review will expand our knowledge of the genomics and epidemiology of Citrobacter spp., enabling improved control of infections and the spread of these organisms.
{"title":"A brief insight into Citrobacter species - a growing threat to public health","authors":"Ishrat Jabeen, Sohidul Islam, A. K. M. I. Hassan, Zerin Tasnim, Sabbir R Shuvo","doi":"10.3389/frabi.2023.1276982","DOIUrl":"https://doi.org/10.3389/frabi.2023.1276982","url":null,"abstract":"Citrobacter spp. are Gram-negative, non-spore forming, rod-shaped, facultative anaerobic bacteria from the Enterobacteriaceae family often found in soil, sewage, sludge, water, food, and the intestinal tracts of animals and humans. Several members of Citrobacter spp. especially C. freundii, C. koseri, C. braakii are frequently detected in newborn illnesses, urinary tract infections, and patients with severe underlying conditions, including hypertension, diabetes, cancer, and respiratory infections, or those who are immunocompromised. Strains of Citrobacter spp. can spread vertically or horizontally from carriers or other hospital sources and thus cause nosocomial infections in hospital settings. A total of 19 Citrobacter genomospecies have been recognized based on genomics. It has been noted that the Citrobacter genus acquired antimicrobial resistance and virulence, including invasion, colonization, biofilm formation, and toxin production. The recent emergence and spread of antimicrobial resistance to β-lactams, carbapenems, fluoroquinolones, aminoglycosides, and colistin in Citrobacter spp. through chromosomal and plasmid-mediated resistance limits the empiric treatment options. Therefore, combination therapy involving costly and potentially hazardous antibiotics poses significant challenges in treating Citrobacter infections. Here we summarized the nomenclature of Citrobacter spp., clinical manifestations, epidemiology, pathogenesis, antibiotic resistance mechanisms, and treatments from various clinical samples. This review will expand our knowledge of the genomics and epidemiology of Citrobacter spp., enabling improved control of infections and the spread of these organisms.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"130 39","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138599058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-06DOI: 10.3389/frabi.2023.1283336
Santi M. Mandal
{"title":"Editorial: Preventative strategies to stop the spread of antibiotic resistance","authors":"Santi M. Mandal","doi":"10.3389/frabi.2023.1283336","DOIUrl":"https://doi.org/10.3389/frabi.2023.1283336","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139322487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-20DOI: 10.3389/frabi.2023.1202256
Patrick Kamalo, Pui-Ying Iroh Tam, Thokozani Noniwa, Chikumbutso Mpanga, Chanizya Mulambia, Ethwako Phiri, Dingase Kumwenda, Ed Phillipo, Samantha Lissauer, David Kulapani, Christina Mwinjiwa
Background Addressing AMR has been most problematic in low- and middle-income countries, which lack infrastructure, diagnostic capacity, and robust data management systems, among other factors. The implementation of locally-led efforts in a low-income country to develop sustainability and build capacity for AMR control within the existing infrastructure has not been well documented. Methods We detail current AMR control initiatives at Queen Elizabeth Central Hospital, a tertiary referral government hospital in Malawi with limited resources, and present the activities accomplished to date, lessons learned, and challenges ahead. Results The key areas of AMR control initiatives that the group focused on included laboratory diagnostics and surveillance, antimicrobial stewardship, infection prevention and control, pharmacy, leadership, education, and funding. Discussion The hospital AMR Control Working Group increased awareness, built capacity, and implemented activities around AMR control throughout the hospital, in spite of the resource limitations in this setting. Our results are based on the substantial leadership provided by the working group and committed stakeholders who have taken ownership of this process. Conclusion Limited resources pose a challenge to the implementation of AMR control activities in low- and middle-income countries. Leadership is central to implementation. Future efforts will need to transition the initiative from an almost fully personal commitment to one with wider engagement to ensure sustainability.
{"title":"Antimicrobial resistance control activities at a tertiary hospital in a low-resource setting: an example of Queen Elizabeth Central Hospital in Malawi","authors":"Patrick Kamalo, Pui-Ying Iroh Tam, Thokozani Noniwa, Chikumbutso Mpanga, Chanizya Mulambia, Ethwako Phiri, Dingase Kumwenda, Ed Phillipo, Samantha Lissauer, David Kulapani, Christina Mwinjiwa","doi":"10.3389/frabi.2023.1202256","DOIUrl":"https://doi.org/10.3389/frabi.2023.1202256","url":null,"abstract":"Background Addressing AMR has been most problematic in low- and middle-income countries, which lack infrastructure, diagnostic capacity, and robust data management systems, among other factors. The implementation of locally-led efforts in a low-income country to develop sustainability and build capacity for AMR control within the existing infrastructure has not been well documented. Methods We detail current AMR control initiatives at Queen Elizabeth Central Hospital, a tertiary referral government hospital in Malawi with limited resources, and present the activities accomplished to date, lessons learned, and challenges ahead. Results The key areas of AMR control initiatives that the group focused on included laboratory diagnostics and surveillance, antimicrobial stewardship, infection prevention and control, pharmacy, leadership, education, and funding. Discussion The hospital AMR Control Working Group increased awareness, built capacity, and implemented activities around AMR control throughout the hospital, in spite of the resource limitations in this setting. Our results are based on the substantial leadership provided by the working group and committed stakeholders who have taken ownership of this process. Conclusion Limited resources pose a challenge to the implementation of AMR control activities in low- and middle-income countries. Leadership is central to implementation. Future efforts will need to transition the initiative from an almost fully personal commitment to one with wider engagement to ensure sustainability.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136313898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-31DOI: 10.3389/frabi.2023.1233698
A. B. Jacobsen, J. Ogden, A. Ekiri
Animals are considered key contributors to the development and spread of antimicrobial resistance (AMR). However, little is known about the existing AMR interventions in the animal sector. This scoping review examines the existing evidence on AMR interventions aimed at livestock, animal health professionals (AHPs), and farmers, while reviewing their impact, limitations, gaps, and lessons for future use. The scoping review was conducted following guidelines from the PRISMA-ScR checklist. The databases, Web of Science, Scopus, PubMed, and international organisations’ websites (WHO, FAO, WOAH) were searched for articles reporting interventions targeting livestock, farmers, and AHPs. Interventions were categorised based on seven pre-defined primary measures including: change in antimicrobial use (AMU) practices; change in the uptake of antimicrobial stewardship (AMS); change in development of AMR; change in knowledge of appropriate AMU practices, AMR, and AMS; change in attitudes and perceptions concerning AMU, AMR, and AMS; and surveillance strategies. In total, ninety three sources were included: 66 studies, 20 reports, and 7 webpages. The reviewed interventions focused mostly on AMU practices (22/90), AMS uptake (8/90), and reduction of bacterial or resistant strains (30/90). Changes in knowledge (14/90) and attitude (1/90) were less frequently assessed and were often implicit. Most interventions were conducted within a select country (83/90) and 7/90 were at a global level. Only 19% (16/83) of interventions were implemented in low- and middle-income countries (LMICs) and most were at herd level with many self-reporting changes. Most of the interventions that focused on surveillance strategies (30/83) were implemented in high-income countries (62/83). Only one study investigated the financial implications of the intervention. The study findings provide an overview of existing AMR interventions and insights into the gaps which can be addressed to guide future interventions and research. A focus on developing, implementing and evaluating interventions in LMICs coupled with the use of objective outcome measures (e.g., measurable outcomes vs. self-reporting) will improve our understanding of the impact of interventions in these settings. Finally, assessing the financial benefits of interventions is necessary to inform feasibility and to encourage uptake of interventions aimed at reducing AMR in the animal health sector.
动物被认为是产生和传播抗菌素耐药性(AMR)的关键因素。然而，人们对动物部门现有的抗菌素耐药性干预措施知之甚少。本范围审查审查了针对牲畜、动物卫生专业人员(ahp)和农民的抗菌素耐药性干预措施的现有证据，同时审查了其影响、局限性、差距和供未来使用的经验教训。范围审查是按照PRISMA-ScR检查表的指导方针进行的。检索了Web of Science、Scopus、PubMed和国际组织的网站(WHO、FAO、WOAH)等数据库，查找报告针对牲畜、农民和ahp的干预措施的文章。干预措施根据七个预先定义的主要措施进行分类，包括:改变抗微生物药物使用(AMU)做法;抗菌药物管理(AMS)吸收的变化;抗菌素耐药性发展的变化;适当的AMU实践、AMR和AMS知识的变化;对AMU、AMR和AMS的态度和认知的改变;以及监控策略。共纳入93个来源:66项研究、20份报告和7个网页。回顾的干预措施主要集中在AMU实践(22/90)、AMS摄取(8/90)和减少细菌或耐药菌株(30/90)。知识(14/90)和态度(1/90)的变化较少被评估，而且往往是隐性的。大多数干预措施是在选定的国家内进行的(83/90)，7/90是在全球一级进行的。只有19%(16/83)的干预措施是在低收入和中等收入国家实施的，而且大多数处于群体水平，存在许多自我报告变化。大多数注重监测战略的干预措施(30/83)是在高收入国家实施的(62/83)。只有一项研究调查了干预的经济影响。研究结果概述了现有的抗菌素耐药性干预措施，并深入了解了可以解决的差距，以指导未来的干预措施和研究。将重点放在制定、实施和评估中低收入国家的干预措施上，并结合使用客观的结果衡量指标(例如，可衡量的结果与自我报告)，将提高我们对这些环境中干预措施影响的理解。最后，有必要评估干预措施的经济效益，以便为可行性提供信息，并鼓励采取旨在减少动物卫生部门抗菌素耐药性的干预措施。
{"title":"Antimicrobial resistance interventions in the animal sector: scoping review","authors":"A. B. Jacobsen, J. Ogden, A. Ekiri","doi":"10.3389/frabi.2023.1233698","DOIUrl":"https://doi.org/10.3389/frabi.2023.1233698","url":null,"abstract":"Animals are considered key contributors to the development and spread of antimicrobial resistance (AMR). However, little is known about the existing AMR interventions in the animal sector. This scoping review examines the existing evidence on AMR interventions aimed at livestock, animal health professionals (AHPs), and farmers, while reviewing their impact, limitations, gaps, and lessons for future use. The scoping review was conducted following guidelines from the PRISMA-ScR checklist. The databases, Web of Science, Scopus, PubMed, and international organisations’ websites (WHO, FAO, WOAH) were searched for articles reporting interventions targeting livestock, farmers, and AHPs. Interventions were categorised based on seven pre-defined primary measures including: change in antimicrobial use (AMU) practices; change in the uptake of antimicrobial stewardship (AMS); change in development of AMR; change in knowledge of appropriate AMU practices, AMR, and AMS; change in attitudes and perceptions concerning AMU, AMR, and AMS; and surveillance strategies. In total, ninety three sources were included: 66 studies, 20 reports, and 7 webpages. The reviewed interventions focused mostly on AMU practices (22/90), AMS uptake (8/90), and reduction of bacterial or resistant strains (30/90). Changes in knowledge (14/90) and attitude (1/90) were less frequently assessed and were often implicit. Most interventions were conducted within a select country (83/90) and 7/90 were at a global level. Only 19% (16/83) of interventions were implemented in low- and middle-income countries (LMICs) and most were at herd level with many self-reporting changes. Most of the interventions that focused on surveillance strategies (30/83) were implemented in high-income countries (62/83). Only one study investigated the financial implications of the intervention. The study findings provide an overview of existing AMR interventions and insights into the gaps which can be addressed to guide future interventions and research. A focus on developing, implementing and evaluating interventions in LMICs coupled with the use of objective outcome measures (e.g., measurable outcomes vs. self-reporting) will improve our understanding of the impact of interventions in these settings. Finally, assessing the financial benefits of interventions is necessary to inform feasibility and to encourage uptake of interventions aimed at reducing AMR in the animal health sector.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48891424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-21DOI: 10.3389/frabi.2023.1179354
Nagendran Tharmalingam, Shi Xu, LewisOscar Felix, B. Roy, M. Xian, E. Mylonakis, B. Fuchs
There is a significant need for new antimicrobial compounds that are effective against drug-resistant microbes. Thioredoxin reductase (TrxR) is critical in redox homeostasis and was identified as a potential drug target and confirmed through inhibition by compounds auranofin and Bay11-7085.Additional TrxR inhibitors were designed and found to exhibit antimicrobial activity against Gram-positive (Enterococcus faecium and Staphylococcus aureus) and glutathione-deficient bacteria (Helicobacter pylori). Investigational compounds were tested for antimicrobial activity, anti-biofilm efficacy, target impact, and cytotoxicity.The first-generation molecules AU1 and AU5 inhibited TrxR activity and inhibited methicillin-resistant S. aureus strain MW2 with minimal inhibitory concentrations (MIC) of 0.125 and 0.5 μg/mL, respectively. In an S. aureus enzymatic assay, AU1 inhibited TrxR enzymatic activity in a dose-dependent manner causing a decrease in intracellular free thiols. In addition, biofilm studies demonstrated that AU1 and AU5 reduced biofilm formation at 1X MIC and disrupted mature biofilms at 4X MIC. Cytotoxicity profiles were created using human cell lines and primary cells with LD50 exceeding MICs by at least 12X.Thus, AU1 and AU5 were TrxR inhibitors that yielded low-concentration antimicrobial activity impacting S. aureus in planktonic and biofilm forms with limited toxic liability.
{"title":"Gold complex compounds that inhibit drug-resistant Staphylococcus aureus by targeting thioredoxin reductase","authors":"Nagendran Tharmalingam, Shi Xu, LewisOscar Felix, B. Roy, M. Xian, E. Mylonakis, B. Fuchs","doi":"10.3389/frabi.2023.1179354","DOIUrl":"https://doi.org/10.3389/frabi.2023.1179354","url":null,"abstract":"There is a significant need for new antimicrobial compounds that are effective against drug-resistant microbes. Thioredoxin reductase (TrxR) is critical in redox homeostasis and was identified as a potential drug target and confirmed through inhibition by compounds auranofin and Bay11-7085.Additional TrxR inhibitors were designed and found to exhibit antimicrobial activity against Gram-positive (Enterococcus faecium and Staphylococcus aureus) and glutathione-deficient bacteria (Helicobacter pylori). Investigational compounds were tested for antimicrobial activity, anti-biofilm efficacy, target impact, and cytotoxicity.The first-generation molecules AU1 and AU5 inhibited TrxR activity and inhibited methicillin-resistant S. aureus strain MW2 with minimal inhibitory concentrations (MIC) of 0.125 and 0.5 μg/mL, respectively. In an S. aureus enzymatic assay, AU1 inhibited TrxR enzymatic activity in a dose-dependent manner causing a decrease in intracellular free thiols. In addition, biofilm studies demonstrated that AU1 and AU5 reduced biofilm formation at 1X MIC and disrupted mature biofilms at 4X MIC. Cytotoxicity profiles were created using human cell lines and primary cells with LD50 exceeding MICs by at least 12X.Thus, AU1 and AU5 were TrxR inhibitors that yielded low-concentration antimicrobial activity impacting S. aureus in planktonic and biofilm forms with limited toxic liability.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44728978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-14DOI: 10.3389/frabi.2023.1176817
Zhengyu Lu, E. Bulut, D. Nydam, R. Ivanek
Antimicrobial resistance (AMR) is a global One Health threat. A portion of AMR development can be attributed to antimicrobial use (AMU) in animals, including dairy cattle. Quantifying AMU on U.S. dairy farms is necessary to inform antimicrobial stewardship strategies and help evaluate the relationship between AMU and AMR. Many AMU indicators have been proposed for quantifying AMU in dairy cattle. However, these indicators are difficult to interpret and compare because they differ in the type of data used, the calculation approach, and the definitions of variables and parameters used in the calculation. Therefore, we selected 16 indicators (count-based, mass-based, and dose-based) applicable for quantifying AMU on U.S. dairy farms. We systematized the indicators by standardizing their variables and parameters to improve their interchangeability, interpretation, and comparability. We scored indicators against six data-driven criteria (assessing their accuracy, data and effort needs, and level of privacy concern) and five stewardship-driven criteria (assessing their ability to capture trends and inform antimicrobial stewardship). The derived standardized indicators will aid farmers and veterinarians in selecting suitable indicators based on data availability and stewardship needs on a farm. The comparison of indicators revealed a trade-off requiring farmers to balance the granularity of data necessary for an accurate indicator and effort to collect the data, and a trade-off relevant to farmers interested in data sharing to inform stewardship because more accurate indicators are typically based on more sensitive information. Indicators with better accuracy tended to score better in stewardship criteria. Overall, two dose-based indicators, estimating the number of treatments and administered doses, scored best in accuracy and stewardship. Conversely, two count-based indicators, estimating the length of AMU, and a mass-based indicator, estimating the mass of administered antimicrobials, performed best in the effort and privacy criteria. These findings are expected to benefit One Health by aiding the uptake of farm-level AMU indicators by U.S. dairy farms.
{"title":"Standardization and evaluation of indicators for quantifying antimicrobial use on U.S. dairy farms","authors":"Zhengyu Lu, E. Bulut, D. Nydam, R. Ivanek","doi":"10.3389/frabi.2023.1176817","DOIUrl":"https://doi.org/10.3389/frabi.2023.1176817","url":null,"abstract":"Antimicrobial resistance (AMR) is a global One Health threat. A portion of AMR development can be attributed to antimicrobial use (AMU) in animals, including dairy cattle. Quantifying AMU on U.S. dairy farms is necessary to inform antimicrobial stewardship strategies and help evaluate the relationship between AMU and AMR. Many AMU indicators have been proposed for quantifying AMU in dairy cattle. However, these indicators are difficult to interpret and compare because they differ in the type of data used, the calculation approach, and the definitions of variables and parameters used in the calculation. Therefore, we selected 16 indicators (count-based, mass-based, and dose-based) applicable for quantifying AMU on U.S. dairy farms. We systematized the indicators by standardizing their variables and parameters to improve their interchangeability, interpretation, and comparability. We scored indicators against six data-driven criteria (assessing their accuracy, data and effort needs, and level of privacy concern) and five stewardship-driven criteria (assessing their ability to capture trends and inform antimicrobial stewardship). The derived standardized indicators will aid farmers and veterinarians in selecting suitable indicators based on data availability and stewardship needs on a farm. The comparison of indicators revealed a trade-off requiring farmers to balance the granularity of data necessary for an accurate indicator and effort to collect the data, and a trade-off relevant to farmers interested in data sharing to inform stewardship because more accurate indicators are typically based on more sensitive information. Indicators with better accuracy tended to score better in stewardship criteria. Overall, two dose-based indicators, estimating the number of treatments and administered doses, scored best in accuracy and stewardship. Conversely, two count-based indicators, estimating the length of AMU, and a mass-based indicator, estimating the mass of administered antimicrobials, performed best in the effort and privacy criteria. These findings are expected to benefit One Health by aiding the uptake of farm-level AMU indicators by U.S. dairy farms.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44942779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-04DOI: 10.3389/frabi.2023.1209552
C.J. Redman-White, D. Moran, A. Peters, A. Muwonge
Antimicrobial resistance (AMR) is a major threat to global health and a key One Health challenge linking humans, animals, and the environment. Livestock are a key target for moderation of antimicrobial use (AMU), which is a major driver of AMR in these species. While some studies have assessed AMU and AMR in individual production systems, the evidence regarding predictors of AMU and AMR in livestock is fragmented, with significant research gaps in identifying the predictors of AMU and AMR common across farming systems. This review summarizes existing knowledge to identify key practices and critical control points determining on-farm AMU/AMR determinants for pigs, layer and broiler hens, beef and dairy cattle, sheep, turkeys, and farmed salmon in Europe. The quality and quantity of evidence differed between livestock types, with sheep, beef cattle, laying hens, turkeys and salmon underrepresented. Interventions to mitigate both AMU and/or AMR highlighted in these studies included biosecurity and herd health plans. Organic production typically showed significantly lower AMU across species, but even in antibiotic-free systems, varying AMR levels were identified in livestock microflora. Although vaccination is frequently implemented as part of herd health plans, its effects on AMU/AMR remain unclear at farm level. Social and behavioral factors were identified as important influences on AMU. The study fills a conspicuous gap in the existing AMR and One Health literatures examining links between farm management practices and AMU and AMR in European livestock production.
{"title":"A review of the predictors of antimicrobial use and resistance in European food animal production","authors":"C.J. Redman-White, D. Moran, A. Peters, A. Muwonge","doi":"10.3389/frabi.2023.1209552","DOIUrl":"https://doi.org/10.3389/frabi.2023.1209552","url":null,"abstract":"Antimicrobial resistance (AMR) is a major threat to global health and a key One Health challenge linking humans, animals, and the environment. Livestock are a key target for moderation of antimicrobial use (AMU), which is a major driver of AMR in these species. While some studies have assessed AMU and AMR in individual production systems, the evidence regarding predictors of AMU and AMR in livestock is fragmented, with significant research gaps in identifying the predictors of AMU and AMR common across farming systems. This review summarizes existing knowledge to identify key practices and critical control points determining on-farm AMU/AMR determinants for pigs, layer and broiler hens, beef and dairy cattle, sheep, turkeys, and farmed salmon in Europe. The quality and quantity of evidence differed between livestock types, with sheep, beef cattle, laying hens, turkeys and salmon underrepresented. Interventions to mitigate both AMU and/or AMR highlighted in these studies included biosecurity and herd health plans. Organic production typically showed significantly lower AMU across species, but even in antibiotic-free systems, varying AMR levels were identified in livestock microflora. Although vaccination is frequently implemented as part of herd health plans, its effects on AMU/AMR remain unclear at farm level. Social and behavioral factors were identified as important influences on AMU. The study fills a conspicuous gap in the existing AMR and One Health literatures examining links between farm management practices and AMU and AMR in European livestock production.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49640147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-02DOI: 10.3389/frabi.2023.1214826
Yogita Thakral
Antimicrobial Resistance (AMR) is one of society’s most urgent global issues, requiring urgent multidisciplinary-based research and practice approaches to engage with these policies. Several global and national policy statements have been released in the last two decades, particularly emphasising the strengthening of the digital surveillance system. However, implementing these initiatives remains patchy, particularly in the context of public health systems in Low- and Middle-Income Countries. This paper argues that one of the significant reasons contributing to this sub-optimal uptake of these systems is that the top-down implementation models do not adequately cater to the needs, aspirations, and capacities of the health facility staff, who, ultimately, are the end users of the system. The paper highlights the importance of digital technology in healthcare facilities with resource constraints to promote the responsible use of antibiotics. It discusses the process of developing an evidence base for action in low- and middle-income countries (LMICs) through digitally mediated data-driven policy. This process is conceptualised as a three-phase process, which involves stabilising data entry, generating outcomes, and taking action at the local level. The paper argues the need for bottom-up implementation models, which emphasise the need to understand the practices users engage with in their everyday work and design the digital system to add value and not work to these everyday practices. The paper emphasises the importance of building local capacities to develop effective and sustainable antimicrobial stewardship (AMS) programs through enabling networking around digital solutions, creating value in networked partnerships, initiating conversations around data, and raising awareness of the digital to develop AMS programs.
{"title":"Digital monitoring for data-driven antimicrobial stewardship: a process perspective from resource-constrained contexts in India","authors":"Yogita Thakral","doi":"10.3389/frabi.2023.1214826","DOIUrl":"https://doi.org/10.3389/frabi.2023.1214826","url":null,"abstract":"Antimicrobial Resistance (AMR) is one of society’s most urgent global issues, requiring urgent multidisciplinary-based research and practice approaches to engage with these policies. Several global and national policy statements have been released in the last two decades, particularly emphasising the strengthening of the digital surveillance system. However, implementing these initiatives remains patchy, particularly in the context of public health systems in Low- and Middle-Income Countries. This paper argues that one of the significant reasons contributing to this sub-optimal uptake of these systems is that the top-down implementation models do not adequately cater to the needs, aspirations, and capacities of the health facility staff, who, ultimately, are the end users of the system. The paper highlights the importance of digital technology in healthcare facilities with resource constraints to promote the responsible use of antibiotics. It discusses the process of developing an evidence base for action in low- and middle-income countries (LMICs) through digitally mediated data-driven policy. This process is conceptualised as a three-phase process, which involves stabilising data entry, generating outcomes, and taking action at the local level. The paper argues the need for bottom-up implementation models, which emphasise the need to understand the practices users engage with in their everyday work and design the digital system to add value and not work to these everyday practices. The paper emphasises the importance of building local capacities to develop effective and sustainable antimicrobial stewardship (AMS) programs through enabling networking around digital solutions, creating value in networked partnerships, initiating conversations around data, and raising awareness of the digital to develop AMS programs.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44415465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-17DOI: 10.3389/frabi.2023.1162941
Andrea M. Binnebose, Adam S Mullis, Shannon L. Haughney, B. Narasimhan, B. Bellaire
Mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in cold-blooded animals and is an opportunistic pathogen in humans. M. marinum is the closest genetic relative of the Mycobacterium tuberculosis complex and is a reliable surrogate for drug susceptibility testing. We synthesized and evaluated two nanoparticle (NP) formulations for compatibility with rifampicin, isoniazid, pyrazinamide, and ethambutol (PIRE), the front-line antimycobacterial drugs used in combination against active tuberculosis infections. Improved in vitro antimicrobial activity was observed with encapsulated rifampicin alone or in a cocktail of drugs formulated through co-encapsulation in amphiphilic polyanhydride NPs. Broth antimicrobial testing revealed that the encapsulation of PIRE in NP resulted in a significant increase in antimicrobial activity, with the benefit over soluble formulations at biologically relevant concentrations ranging from >10 to >3,000 fold. M. marinum-infected human macrophages treated with NP-PIRE were cleared of viable bacteria in 48 h following a single treatment, representing a >4 log reduction in colony-forming units and a >2,000-fold increase in antimicrobial activity. The amphiphilic polyanhydride nanoparticles demonstrated the ability to co-encapsulate PIRE antibiotics and enhance their antimicrobial activity against M. marinum in infected macrophages in culture and in vitro. These data suggest that polyanhydride nanoparticles are a promising nanotherapeutic for combatting Mycobacterium infections through improved intracellular targeting of encapsulated antibiotics.
{"title":"Nanotherapeutic delivery of antibiotic cocktail enhances intra-macrophage killing of Mycobacterium marinum","authors":"Andrea M. Binnebose, Adam S Mullis, Shannon L. Haughney, B. Narasimhan, B. Bellaire","doi":"10.3389/frabi.2023.1162941","DOIUrl":"https://doi.org/10.3389/frabi.2023.1162941","url":null,"abstract":"Mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in cold-blooded animals and is an opportunistic pathogen in humans. M. marinum is the closest genetic relative of the Mycobacterium tuberculosis complex and is a reliable surrogate for drug susceptibility testing. We synthesized and evaluated two nanoparticle (NP) formulations for compatibility with rifampicin, isoniazid, pyrazinamide, and ethambutol (PIRE), the front-line antimycobacterial drugs used in combination against active tuberculosis infections. Improved in vitro antimicrobial activity was observed with encapsulated rifampicin alone or in a cocktail of drugs formulated through co-encapsulation in amphiphilic polyanhydride NPs. Broth antimicrobial testing revealed that the encapsulation of PIRE in NP resulted in a significant increase in antimicrobial activity, with the benefit over soluble formulations at biologically relevant concentrations ranging from >10 to >3,000 fold. M. marinum-infected human macrophages treated with NP-PIRE were cleared of viable bacteria in 48 h following a single treatment, representing a >4 log reduction in colony-forming units and a >2,000-fold increase in antimicrobial activity. The amphiphilic polyanhydride nanoparticles demonstrated the ability to co-encapsulate PIRE antibiotics and enhance their antimicrobial activity against M. marinum in infected macrophages in culture and in vitro. These data suggest that polyanhydride nanoparticles are a promising nanotherapeutic for combatting Mycobacterium infections through improved intracellular targeting of encapsulated antibiotics.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44409791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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