Challenge Of Antimicrobial Resistance Research Articles

Knowledge, attitudes, and practices on camel respiratory diseases and conditions in Garissa and Isiolo, Kenya.

Livestock farmers' attitudes, practices, and behaviors are major factors in infection prevention and control of animal diseases. Kenya has the fourth largest global camel population, and the industry has grown over the last two decades, transforming beyond the traditional camel-keeping areas to include peri-urban camel trade and value chain growth. The dromedary camel is resilient, and it is a preferred species in the arid and semi-arid areas (ASALs) of Kenya. However, it still faces many health and production challenges; to identify infection drivers and risky behaviors for camel respiratory illnesses and conditions in Kenya, we conducted a knowledge, attitudes, and practices (KAP) survey. Using a set of tools (questionnaires, key informant interviews, and focus group discussions), we interviewed camel owners, herders, agro-veterinary outlets, and other relevant value chain stakeholders in Garissa and Isiolo counties (n = 85). Data were analyzed using descriptive and analytic statistics. Most camel owners/herders are male and most are relatively uneducated (85.5%). The camels were used primarily for milk and meat production, income generation, and transport. Larger herd sizes (>30 camels) and owner/herder's lack of formal education are risk factors for owner-reported respiratory illnesses in camels. Major clinical signs of respiratory conditions were coughing (85.7%), nasal discharge (59.7%), and fever (23.4%). Diseases, lack of feeds, theft, and marketing challenges are the major constraints to camel production in Kenya. Owners-herders use drugs indiscriminately and this may contribute to antimicrobial resistance challenges. Practitioners in the camel value chain want more commitment from the government and animal health officials on support services and access to veterinary services. Watering points, grazing areas, and marketing points are the primary areas for congregating camels and have a significant potential for disease spread. Kenya camels have a massive capacity for rural and ASALs' livelihoods transformation but the identified health challenges, and other issues must be addressed. Further studies on the Kenyan camels' respiratory microbial ecology are important to understand microbial risks and reduce the burden of zoonotic infections. Intensification of risk communication and community engagement, and messaging targeted at behavior change interventions should be directed at camel value chain actors.

Mcr-1 colistin resistance gene sharing between Escherichia coli from cohabiting dogs and humans, Lisbon, Portugal, 2018 to 2020.

BackgroundThe emergence of colistin resistance is a One Health antimicrobial resistance challenge worldwide. The close contact between companion animals and humans creates opportunities for transmission and dissemination of colistin-resistant bacteria.AimTo detect potential animal reservoirs of colistin-resistant Escherichia coli and investigate the possible sharing of these bacteria between dogs, cats and their cohabiting humans in the community in Lisbon, Portugal.MethodsA prospective longitudinal study was performed from 2018 to 2020. Faecal samples from dogs and cats either healthy or diagnosed with a skin and soft tissue or urinary tract infection, and their cohabiting humans were screened for the presence of colistin-resistant E. coli. All isolates were tested by broth microdilution against colistin and 12 other antimicrobials. Colistin-resistant isolates were screened for 30 resistance genes, including plasmid-mediated colistin resistance genes (mcr-1 to mcr-9), and typed by multilocus sequence typing. Genetic relatedness between animal and human isolates was analysed by whole genome sequencing.ResultsColistin-resistant E. coli strains harbouring the mcr-1 gene were recovered from faecal samples of companion animals (8/102; 7.8%) and humans (4/125; 3.2%). No difference between control and infection group was detected. Indistinguishable multidrug-resistant E. coli ST744 strains harbouring the mcr-1 gene were found in humans and their dogs in two households.ConclusionsThe identification of identical E. coli strains containing the plasmid-mediated mcr-1 gene in companion animals and humans in daily close contact is of concern. These results demonstrate the importance of the animal-human unit as possible disseminators of clinically important resistance genes in the community setting.

Synergistic Combination of Biodegradable Peptide Polymer and Curcumin as Promising Antibiotic Substitution in Aquaculture to Alleviate the Global Challenge of Antimicrobial Resistance

Comprehensive SummaryThe massive use of antibiotics in aquaculture and resulted antibacterial resistance problem urgently need antibiotic substitutions. Herein, we report a promising substitution of aquaculture antibiotics using a synergistic combination of biodegradable peptide polymers and curcumin, a natural compound from plant. The synergistic combination shows strong antibacterial activity against V. fluvialis and some other common bacteria in aquaculture. The membrane‐damaging antibacterial mechanism echoes our finding that the synergistic combination will not induce bacteria to develop resistance after continuous use. The synergistic combination also displays effective cure on V. fluvialis‐infected zebrafish. The biodegradability of the peptide polymer enables the combination to lose antibacterial activity and will not cause selective pressure on bacterial in the environment. Our study indicates potential application of synergistic composition, biodegradable peptide polymer and curcumin, as promising antibiotic substitution in aquaculture, which represents a promising strategy to address the global challenge of antimicrobial resistance.

Influencing mechanism of the use behavior of clinical practice guidelines on antimicrobials: evidence from the integration of theory of reasoned action and organizational readiness for change

BackgroundTo confront the serious challenge of antimicrobial resistance, using clinical practice guidelines (CPGs) standardizing the prescription behavior is vital. However, the overall mechanisms remains largely unknown as to how guidelines' use behavior can be improved. This study aimed to identify the determinants and investigate their relationship to bridge the knowledge gap of overall influencing mechanism of the use behavior of CPGs on antimicrobials.MethodsBy integrating theory of reasoned action (TRA) and organizational readiness for change (ORC), a structured questionnaire was developed to cover potential determinants that affect physicians’ use behaviors of CPGs on antimicrobials at the individual-level (attitude, subjective norm, and behavioral intention) and organizational-level (top management support and organizational resource allocation). A multi-stage random sampling was implemented to collect data from physicians in secondary and tertiary hospitals from eastern, central and western China. Structural equation model (SEM) was used to test the proposed hypotheses, and to analyze the relationship and mechanism among the factors.ResultIn total, 815 physicians were included. Most physicians demonstrated a positive tendency toward the use of CPGs on antimicrobials, with a mean score of 3.95 (SD = 0.70). The reliability and validity analysis showed the questionnaire constructed from the integrated theoretical model of TRA and ORC was acceptable. The SEM validation results also showed that the top management support (β = 0.688, P < 0.001), organizational resource allocation (β = 0.129, P < 0.001), individual attitudes (β = 0.164, P < 0.001), subjective norms (β = 0.322, P < 0.001), and behavioral intentions (β = 0.424, P < 0.001) were positively associated with physicians’ use behaviors of CPGs on antimicrobials. Besides, top management support, organizational resource allocation, attitudes and subjective norms showed their mediating effects on regarding use behavior, which was 0.305, 0.129, 0.164 and 0.201, respectively.ConclusionsThis study revealed the influence mechanism of the use of CPGs on antimicrobials from the individual and organizational perspectives. These findings will not only help formulate future strategies to promote the use of CPGs on antimicrobials, but also provide clues for more effective prescription interventions.

2.B. Round table: Rethinking innovation systems to meet the challenges of AMR: Lessons from the Covid-19 pandemic

Abstract Innovations have always been essential to solving our most pressing public health issues - from diagnostics to vaccines, to various therapeutics including antimicrobials. The ability of innovations to improve public health depends on the wider healthcare innovation systems that frame their development, uptake and diffusion. These innovation systems are made up of diverse actors including researchers and innovators in the public sector and industry, regulators, international bodies, not-for-profits, investors, healthcare professionals and patients and the public. However, the needs and interests of these diverse actors do not always align, nor do innovations systems always align with societal needs, particularly where there are market failures. Antimicrobial resistance (AMR) is an example of a public health issue that is challenging to solve within existing innovation systems, as incentive structures for developing and (not inappropriately) using antimicrobials are not sufficient to address the threat of growing resistance. In this workshop, we will facilitate a discussion of how innovation systems can be rethought to better align with societal needs, with a specific focus on how learning from the Covid-19 pandemic may be applied to innovation in response to the “silent pandemic” of AMR. This type of discussion matters greatly for tackling one of the most pressing public health challenges of our time and for harnessing the potential for timely learning and action. This panel discussion is co-hosted by RAND Europe and the European Observatory on Health Systems and Policy. Researchers from RAND Europe will first introduce the session and present key insights from their recent research on AMR-relevant innovation and lessons from the Covid-19 pandemic. This will provide the foundation for a panel discussion in which panelists will share their expertise and views on what lessons from the Covid-19 response mean for AMR and how these lessons can be feasibly applied to AMR-relevant innovation. Some areas for reflection include economic push and pull incentives, regulation, surveillance, data-sharing and data linkage, public-private collaboration, awareness raising and political will. Throughout the session, we will encourage participation from the audience and will ask participants to identify relevant questions in small groups at the beginning of the session. In bringing together diverse voices (on the panel and in the audience) that approach the innovation system from different angles, we hope to build an understanding of how the innovation system and mechanisms by which it operates can work better for everyone and tackle the urgent societal challenge of AMR, as well as explore whether any of the insights gained may apply more widely to other pressing public health challenges where there are market failures. Key messages • Participants will gain a better understanding of how aspects of the Covid-19 response may be transferrable or adaptable to AMR-relevant innovation and how this can be achieved in a timely manner. • Participants will identify needs for further research, policy and action to support innovation systems that are more responsive to AMR needs and potentially also to other public health challenges. Speakers/ Panellists Sonja Marjanovic RAND Europe, Cambridge, UK Sarah Parkinson RAND Europe, Cambridge, UK Nick Fahy RAND Europe, Cambridge, UK Dimitra Panteli European Observatory on Health Systems and Policies, Brussels, Belgium Michael Anderson London School of Economics and Political Science, Birmingham, UK

Typhoid fever control in the 21st century: where are we now?

Momentum for achieving widespread control of typhoid fever has been growing over the past decade. Typhoid conjugate vaccines represent a potentially effective tool to reduce the burden of disease in the foreseeable future and new data have recently emerged to better frame their use-case. We describe how antibiotic resistance continues to pose a major challenge in the treatment of typhoid fever, as exemplified by the emergence of azithromycin resistance and the spread of Salmonella Typhi strains resistant to third-generation cephalosporins. We review efficacy and effectiveness data for TCVs, which have been shown to have high-level efficacy (≥80%) against typhoid fever in diverse field settings. Data from randomized controlled trials and observational studies of TCVs are reviewed herein. Finally, we review data from multicountry blood culture surveillance studies that have provided granular insights into typhoid fever epidemiology. These data are becoming increasingly important as countries decide how best to introduce TCVs into routine immunization schedules and determine the optimal delivery strategy. Continued advocacy is needed to address the ongoing challenge of typhoid fever to improve child health and tackle the rising challenge of antimicrobial resistance.

Emotive Themes from Tennessee Cattle Producers Regarding Responsible Antibiotic Use.

Simple SummaryUnderstanding the emotional experiences of producers towards their antimicrobial use (AMU) practices can be a starting point to making future behavioral changes that could reduce the emergence of antimicrobial resistance challenge. Between June 2017 and March 2018, seven focus group meetings of Tennessee (TN) beef and dairy cattle producers were conducted to evaluate producers’ emotional views regarding responsible AMU in cattle. Sixty-two TN cattle producers participated and emotively expressed the following: (1) deep connections to animals in ways that improve animal and public health; (2) pride in their quality of products; (3) distress that consumers misconceive their AMU practices as indiscriminate; and (4) recommended that producers be more transparent about their AMU practices and the public improve their awareness for detecting marketers’ deceptive product labels that take advantage of public ignorance. Knowledge of these producers’ emotions would help educators target more successful behavioral change campaigns, improving stewardship in AMU practices among producers.To improve judicious antimicrobial use (AMU) in food animals in the United States, all feed additives that were medically important antimicrobials were moved from over the counter to Veterinary Feed Directive in 2017. This action required a change in behavior of producers’ AMU practices. Because emotions are important aspects of behavior, several behavioral interventions have targeted people’s emotions as means of effecting change. Hence, understanding and incorporating the emotional experiences of producers towards current AMU practices can be a starting point to making future behavioral changes that could reduce the emergence of antimicrobial resistance challenge. Between June 2017 and March 2018, seven focus group meetings of Tennessee (TN) beef and dairy cattle producers were conducted to evaluate producers’ emotional views regarding responsible AMU in TN cattle. Sixty-two TN cattle producers participated and emotively expressed the following: (1) deep connections to animals in ways that improve animal and public health; (2) pride in their quality of products; (3) distress that consumers misconceive their AMU practices as indiscriminate; and (4) recommended that producers be more transparent about their AMU practices and the public improve their awareness for detecting marketers’ deceptive product labels that take advantage of public ignorance. Knowledge of these producers’ emotions would help educators target more successful behavioral change campaigns, improving stewardship in AMU practices among producers.

Structural modification and antibacterial property studies of natural chalcone sanjuanolide.

Clinical infections arise from multidrug-resistant bacteria and pose a serious threat to human and global public health. Moreover, due to very few antibiotics being discovered, there is an urgent need to develop new antibacterial agents to combat antimicrobial resistance challenges. In this study, a series of new chalcone derivatives bearing a 3′-hydroxyisoprenyl moiety were prepared to employ Claisen–Schmidt condensation as a key step by combinatorial chemistry, and overall yields of these novel derivatives are in the range of 28–68% in the two-step reaction. Sanjuanolide and the synthesized derivatives have been investigated for their expected antibacterial activities against Gram-positive bacteria (Staphylococcus aureus CMCC 26003) and Gram-negative bacteria (Escherichia coli CMCC 44102). Among these compounds, only 4c (MIC = 12.5 μg/ml) and 4d (MIC = 25 μg/ml) exhibited antibacterial activity comparable to sanjuanolide (MIC = 12.5 μg/ml, against S. aureus CMCC 26003), and the results of subsequent in vivo experiments on sanjuanolide suggest that sanjuanolide exhibits bacteriostatic and bactericidal effects by altering the cellular structure, disrupting the integrity of cell membranes, and reducing the outer membrane potential.

Combating antimicrobial resistance in neonatal infections: a South African perspective

The challenge of antimicrobial resistance in neonatal infections in low-income and middle-income countries requires attention. The Article by Rudzani C Mashau and colleagues in The Lancet Global Health provides insights into invasive neonatal infections, including antimicrobial resistance, within the South African public health sector.1 Of note, widespread antimicrobial resistance among neonates, at a population level, has been reconfirmed.

System Mapping of Antimicrobial Resistance to Combat a Rising Global Health Crisis.

Antimicrobial resistance (AMR) decreases the effectiveness of antimicrobials to treat bacterial infections in humans and animals. The increased occurrence of AMR in bacterial population in humans, animals, and the environment requires the measures to combat a rising global health crisis. The aim of this research was to present current knowledge on AMR in a system map and to identify potential explanations of former identified variables significantly associated with AMR. This study applies a systems thinking approach and uses feedback loops to visualize the interconnections between human, animal, and environmental components in a circular AMR system map model. First, a literature review focusing on AMR and socioeconomic factors, wicked problem, and system change was carried out, which was then processed in a system map to conceptualize the present core challenges of AMR via feedback loops. Second, to investigate possible underlying values of the society and those that influence humans' behavior in the present AMR system, an iceberg model was established. Third, leverage points were assessed to estimate which kinds of interventions would have the greatest effect to mitigate AMR in the system. The present AMR system map implies the potential to identify and visualize important risk factors that are direct or indirect drivers of AMR. Our results show that the tool of system mapping, which interconnects animals, humans, and environment in one model, can approach AMR holistically and be used to assess potential powerful entry points for system wide interventions. This study shows that system maps are beneficial as a model to predict the relative effect of different interventions and adapt to rapidly changing environments in a complex world. Systems thinking is considered as a complementing approach to the statistical thinking, and further research is needed to evaluate the use of such tools for the development and monitoring of interventions.

A study on the clinical spectrum, prescription pattern and diagnosis of enteric fever in a tertiary care hospital of North India

Background: Enteric fever is a major public health concern in developing countries. Lack of diagnostics diagnosis and antimicrobial resistance challenges in treatment of enteric fever. Timely diagnosis and proper management of fever are essential to reduce the complications and emergence antibiotic resistance.Methods: A prospective observational study was conducted on 71 subjects between February 2018 and December 2019. Spectrum of the disease, antimicrobial resistance and prescription pattern were observed and performances of various diagnostic methods (like culture, serology and loop mediated isothermal amplification) were determined.Results: The most commonly observed clinical features included gastrointestinal complaints, anaemia, leukopenia, splenomegaly and hepatitis. Blood culture was positive for 49.3% (35/71) of the cases using conventional culture method. All samples positive by LAMP were also culture positive, out of which 80% (28/35) were S. typhi and 20% (7/35) were S. paratyphi A. Antimicrobial susceptibility to ciprofloxacin was 39.3% and 28.6% and ampicillin susceptibility was 32.1 and 28.6% in S. typhi and S. paratyphi A respectively. Only one multidrug resistant isolate was noted, while none was resistant to ceftriaxone or azithromycin. Cefixime and azithromycin combination therapy led to the earliest defervescence of fever.Conclusions: Oral combination therapy may be a good option to treat enteric fever and oral combination therapy may be a good option to treat enteric fever and performance of LAMP seem to be as good as culture with a shorter turnaround time. LAMP can be used to obviate the need of culture in resource limited settings.

Ruminant health research – progress to date and future prospects, with an emphasis on Irish research

This review addresses the progress that has been made in ruminant health research over the last 60 yr, with an emphasis on Irish research. The review focuses on the economically important infectious diseases of dairy and beef cattle and of sheep, calf diseases, regulated and non-regulated infectious diseases, lameness, mastitis and parasitoses. The progress to date, current knowledge and future challenges are all addressed. Paradigm shifts have occurred in many of these diseases, the most profound of which is the change from increasing antimicrobial usage (AMU) to the realisation of the challenge of antimicrobial resistance (AMR) and the current reduction in AMU. Another major change in thinking is the move away from focus on the pathogen exclusively towards a more holistic view of the roles of host immunity and adequacy of management. In the last 60 yr, many new diseases have emerged but in parallel many new technologies have rapidly evolved to monitor and control these threats to animal health. Irish research has contributed substantially to improved current ruminant health. The major future challenge is how to manage ruminant health in a OneHealth world where animal, human and environmental health and sustainability are intimately intertwined and interdependent.

Challenges of Antimicrobial Resistance and Stewardship in Solid Organ Transplant Patients.

Purpose of ReviewWithout effective antimicrobials, patients cannot undergo transplant surgery safely or sustain immunosuppressive therapy. This review examines the burden of antimicrobial resistance in solid organ transplant recipients and identifies opportunities for antimicrobial stewardship.Recent FindingsAntimicrobial resistance has been identified to be the leading cause of death globally. Multidrug-resistant pathogens are associated with significant morbidity and mortality in transplant recipients. Methicillin-resistant S. aureus affects liver and lung recipients, causing bacteremia, pneumonia, and surgical site infections. Vancomycin-resistant enterococci is a nosocomial pathogen primarily causing bacteremia in liver recipients. Multidrug-resistant Gram-negative pathogens present urgent and serious threats to transplant recipients. Extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae commonly cause bacteremia and intra-abdominal infections in liver and kidney recipients. Carbapenemase-producing Enterobacterales, mainly K. pneumoniae, are responsible for infections early-post transplant in liver, lung, kidney, and heart recipients. P. aeruginosa and A. baumannii continue to be critical threats. While there are new antimicrobial agents targeting resistant pathogens, judicious prescribing is crucial to minimize emerging resistance. The full implications of the COVID-19 global pandemic on antimicrobial resistance in transplant recipients remain to be understood. Currently, there are no established standards on the implementation of antimicrobial stewardship interventions, but strategies that leverage existing antimicrobial stewardship program structure while tailoring to the needs of transplant recipients may help to optimize antimicrobial use.SummaryClinicians caring for transplant recipients face unique challenges tackling emerging antimcirobial resistance. Coordinated antimicrobial stewardship interventions in collaboration with appropriate expertise in transplant and infectious diseases may mitigate against such threats.

Assessment of Farmer’s Knowledge of Antimicrobial Resistance, Their Practice of Antimicrobial Usage and Biosecurity Status of Poultry Farms in Kathmandu Valley and Chitwan District, Nepal

The poultry industry has transformed into one of the vibrant economic activities in Nepal, contributing to almost 4% of the national GDP. We conducted a cross-sectional survey among the poultry farmers of Kathmandu valley and Chitwan district to assess their knowledge of antimicrobial resistance (AMR); their practice of antimicrobial usage and the biosecurity status of their poultry farms. The survey was done to understand the level of knowledge gap among the farmers regarding successful poultry farming with strict biosecurity protocol and minimal use of antibiotics. A semi-structured questionnaire was prepared to interview a total of 112 farmers, with 56 respondents from each study sites. Only nineteen percent (11/56) of the farmers from the Kathmandu valley and 16% (9/56) of that of Chitwan district knew about the antimicrobial resistance (AMR). Doxycycline (25.9%, 29/112) was the most used antibiotic followed by Tylosin (21.5%, 24/112), Colistin (18.75%, 21/112), Ciprofloxacin (13.4%, 15/112) and Neomycin (12.5%, 14/112) in both districts. Majority of the surveyed respondents lacked the proper awareness regarding the importance of considerate use of antimicrobial drugs, effectiveness of implementing proper biosecurity protocols in the farms, and the increasing challenge of AMR in the present world scenario. The findings and results of this survey identify the critical gaps in the knowledge of the farmers concerning the day-to-day operations in their poultry business. Immediate strategic actions and road-maps are required to solve the burgeoning problem of AMR considering the imprudent use of antibiotics in the poultry sector. Int. J. Appl. Sci. Biotechnol. Vol 10(1): 50-59.

Pharmacodynamics of Meropenem and Tobramycin for Neonatal Meningoencephalitis: Novel Approaches to Facilitate the Development of New Agents to Address the Challenge of Antimicrobial Resistance.

Neonatal sepsis is an underrecognized burden on health care systems throughout the world. Antimicrobial drug resistance (AMR) is increasingly prevalent and compromises the use of currently recommended first-line agents. The development of new antimicrobial agents for neonates and children is mandated by regulatory agencies. However, there remains uncertainty about suitable development pathways, especially because of the propensity of premature babies to develop meningoencephalitis as a complication of neonatal sepsis and difficulties studying this disease in clinical settings. We developed a new platform and approach to accelerate the development of antimicrobial agents for neonatal bacterial meningoencephalitis using Pseudomonas aeruginosa as the challenge organism. We defined the pharmacodynamics of meropenem and tobramycin in these models. The percentage of partitioning of meropenem and tobramycin into the cerebrospinal fluid was comparable at 14.3 and 13.7%, respectively. Despite this similarity, there were striking differences in their pharmacodynamics. Meropenem resulted in bactericidal activity in both the cerebrospinal fluid and cerebrum, whereas tobramycin had minimal antibacterial activity. A hollow fiber infection model (HFIM) using neonatal CSF concentration time profiles yielded pharmacodynamics comparable to those observed in the rabbit model. These new experimental models can be used to estimate the pharmacodynamics of currently licensed agents and those in development and their potential efficacy for neonatal bacterial meningoencephalitis.

The Collateral Effects of COVID-19 Pandemic on the Status of Carbapenemase-Producing Pathogens.

The serious challenge of antimicrobial resistance continues to threaten public health and lingers in the era of the coronavirus disease 2019 (COVID-19), declared pandemic by the World Health Organization. While the pandemic has triggered the importance of infection control practices and preventive measures such as physical distancing, hand hygiene, travel reduction and quarantine, the ongoing alarm of antimicrobial resistance seems to accompany the pandemic too. Antimicrobial resistance has been fostered during COVID-19, possibly due to high rate of empirical antibiotic utilization in COVID-19 patients, increased use of biocides, and the disruption of proper healthcare for other conditions. Specifically, carbapenemase-producing Gram-negative bacteria have shown to cause secondary bacterial infections in patients hospitalized for COVID-19. Clinical and microbiological evidence of such infections is accumulating in different parts of the world. With the resilient nature of carbapenemases, their association with mortality, and the limited treatment options available, concerns regarding this group of antibiotic-hydrolyzing enzymes during the pandemic are expected to upsurge. While the additional burden carbapenemases exert on healthcare is worrisome, it remains hidden or abandoned among the various health consequences of the pandemic. The purpose of this minireview is to shed a light on carbapenemase-associated infections during such unprecedented time of COVID-19. A focused insight shall be made into carbapenemases, their implications for COVID-19 patients, and the features and consequences of co-infection, with a review of available evidence from pertinent literature. The importance of increased surveillance for carbapenemase-producers and optimizing their management in relation to the pandemic, shall be addressed as well.

An ultrasensitive microfluidic approach reveals correlations between the physico-chemical and biological activity of experimental peptide antibiotics

Antimicrobial resistance challenges the ability of modern medicine to contain infections. Given the dire need for new antimicrobials, polypeptide antibiotics hold particular promise. These agents hit multiple targets in bacteria starting with their most exposed regions—their membranes. However, suitable approaches to quantify the efficacy of polypeptide antibiotics at the membrane and cellular level have been lacking. Here, we employ two complementary microfluidic platforms to probe the structure–activity relationships of two experimental series of polypeptide antibiotics. We reveal strong correlations between each peptide’s physicochemical activity at the membrane level and biological activity at the cellular level. We achieve this knowledge by assaying the membranolytic activities of the compounds on hundreds of individual giant lipid vesicles, and by quantifying phenotypic responses within clonal bacterial populations with single-cell resolution. Our strategy proved capable of detecting differential responses for peptides with single amino acid substitutions between them, and can accelerate the rational design and development of peptide antimicrobials.

'She Wanted to Listen to her General Practitioner's Advice…': Exploring and Explaining Antibiotic Prescribing as a Regulatory Encounter.

This article examines the pressing global problem of antimicrobial resistance (AMR), applying motivational posture theory to demonstrate how AMR and the prescribing that drives it can be considered a regulatory challenge. Following an outline of AMR and the threat of the 'superbugs' to which it gives rise, the article assesses the regulatory nature of the 'prescribing encounter' in the primary care setting. It applies both a responsive regulatory lens and motivational posture theory to analyse over 100 narrative accounts of encounters between a general practitioner and a patient. In so doing, the article examines the discursive repertoires and cultural resources available to primary care patients to explain the prescribing encounter and the dynamics within it. It concludes that patients conceive of prescribers as regulatory authorities and prescribing itself as a regulatory encounter. On this basis, the article argues that applying responsive regulatory theory and practice in response to the AMR challenge is likely to find reasonable patient acceptance, offering a new approach to this currently intractable challenge. This article then offers an analysis of what factors indicate patient drift towards defiance of regulatory aims, and what engagement and support encourage a return to cooperation.

Identification of β-Lactams Active against Mycobacterium tuberculosis by a Consortium of Pharmaceutical Companies and Academic Institutions.

Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill & Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories. We developed a higher order consortium within the TBDA in which four pharmaceutical companies (GlaxoSmithKline, Sanofi, MSD, and Lilly) collectively collaborated with screeners at Weill Cornell Medicine, the Infectious Disease Research Institute (IDRI), and the National Institute of Allergy and Infectious Diseases (NIAID), pharmacologists at Rutgers University, and medicinal chemists at the University of North Carolina to screen ∼8900 β-lactams, predominantly cephalosporins, and characterize active compounds. In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-lactamase inhibitor. One potent cephaloporin was active in Mtb-infected mice. The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents.

Evaluating the Role of Veterinarians in the One Health Approach to Antimicrobial Resistance in Jordan

Background Antimicrobials, including antibiotics, antivirals, antifungals, and antiparasitics, are drugs used to prevent and treat infections in humans, animals, and plants. Objective This study aimed to evaluate the role of knowledge, attitudes, and practices of Jordanian veterinarians in combating antimicrobial resistance (AMR), and to summarize the registered veterinary drugs between 2017 and 2020. Methods The descriptive study data were collected using a standardized questionnaire focusing on knowledge, attitudes, and practices of Jordanian veterinarians. Results The results were analyzed descriptively and showed that the mean knowledge of the participants who agreed with the statement on AMR definition was 84%. The majority (95.65%) agreed that AMR is a challenge for the veterinary sector in Jordan and should be prioritized among other zoonotic diseases. Around 69% of the participants believe that the misuse and overuse of antimicrobials by quacks—fraudulent and unauthorized practitioners—are the main reasons for AMR challenge. The most common practice among the respondents was recommending clients (farmers, owners, etc) to practice good animal husbandry (80%). The study also revealed that there was a significant difference (P=.02) between attending training about AMR and their professional sector (private, public, and academic). Conclusions This study showed the importance of implementing a continuous education program on antimicrobial resistance to improve veterinarians’ knowledge in all aspects of antimicrobial resistance and to increase their advisory skills. Laws should also be enacted to ensure that veterinarians prescribe the correct antimicrobials and improve the surveillance system to monitor the use of antimicrobials in veterinary medicine.