scholarly journals Discovery and development of new antimicrobial agents.

1990 ◽  
Vol 3 (1) ◽  
pp. 13-31 ◽  
Author(s):  
T D Gootz
Keyword(s):  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Bacterial Cells ◽  
Beta Lactams ◽  
Resistance Development ◽  
Safety Testing ◽  
The Past ◽  
Body Of Knowledge ◽  
New Antibiotics ◽  
The Impact

The unprecedented growth in the number of new antibiotics over the past two decades has been the result of extensive research efforts that have exploited the growing body of knowledge describing the interactions of antibiotics with their targets in bacterial cells. Information gained from one class of antimicrobial agents has often been used to advance the development of other classes. In the case of beta-lactams, information on structure-activity relationships gleaned from penicillins and cephalosporins was rapidly applied to the cephamycins, monobactams, penems, and carbapenems in order to discover broad-spectrum agents with markedly improved potency. These efforts have led to the introduction of many new antibiotics that demonstrate outstanding clinical efficacy and improved pharmacokinetics in humans. The current review discusses those factors that have influenced the rapid proliferation of new antimicrobial agents, including the discovery of new lead structures from natural products and the impact of bacterial resistance development in the clinical setting. The development process for a new antibiotic is discussed in detail, from the stage of early safety testing in animals through phase I, II, and III clinical trials.

scholarly journals Blocking the Trigger: Inhibition of the Initiation of Bacterial Chromosome Replication as an Antimicrobial Strategy

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 111
Author(s):  
Julia E. Grimwade ◽  
Alan C. Leonard
Keyword(s):  
Drug Targets ◽  
Antimicrobial Agents ◽  
Current Knowledge ◽  
Chromosome Replication ◽  
Bacterial Chromosome ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Drug Resistant Bacteria ◽  
New Antibiotics ◽  
Novel Drug

All bacterial cells must duplicate their genomes prior to dividing into two identical daughter cells. Chromosome replication is triggered when a nucleoprotein complex, termed the orisome, assembles, unwinds the duplex DNA, and recruits the proteins required to establish new replication forks. Obviously, the initiation of chromosome replication is essential to bacterial reproduction, but this process is not inhibited by any of the currently-used antimicrobial agents. Given the urgent need for new antibiotics to combat drug-resistant bacteria, it is logical to evaluate whether or not unexploited bacterial processes, such as orisome assembly, should be more closely examined for sources of novel drug targets. This review will summarize current knowledge about the proteins required for bacterial chromosome initiation, as well as how orisomes assemble and are regulated. Based upon this information, we discuss current efforts and potential strategies and challenges for inhibiting this initiation pharmacologically.

scholarly journals Antimicrobial and Antioxidant Activities of Extracts and Compounds From Trifolium Baccarinii With Their Mechanisms of Antibacterial Action

2020 ◽  
Author(s):  
Léonel Feugap ◽  
Irene Kengne ◽  
Jean-De-Dieu Tamokou ◽  
Claudia Ngnokam ◽  
Mahamat Djamalladine ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Higher Plants ◽  
Antioxidant Activities ◽  
Antioxidant Defenses ◽  
Biochanin A ◽  
Antibacterial Action ◽  
Bacterial Cells ◽  
Whole Plant

Abstract The treatment of infectious diseases with antimicrobial agents continues to present problems in modern-day medicine with many studies showing significant increase in the incidence of bacterial resistance to several antibiotics. The screening of plant extracts and natural compounds for antimicrobial activity has demonstrated that higher plants represent a potential source of new anti-infective agents. The aim of this study was to evaluate the antimicrobial and antioxidant activities of extracts and compounds from the whole plant Trifolium baccarinii Chiov. with their mechanisms of antibacterial action. Biochanin A (1), formononetin (2), luteolin (3), luteolin-4'-O-β-D-glucopyranoside (4), 4,7,2'-trihydroxy-4'-methoxyisoflavanol (5), sissotrin (6), 1-méthyl-β-D-glucopyranoside (7), ononin (8), D-mannitol (9) and 3-O-β-D-glucuronopyranosylsoyasapogenol B (10) were isolated from T. baccarinii. The MeOH, EtOAc and n-BuOH extracts as well as compounds 1–6 from T. baccarinii displayed the most antimicrobial and antioxidant activities. The MeOH extract and compound 5 exhibited antibacterial activity through bacteriolytic effect and reduction of the antioxidant defenses in the bacterial cells. Interestingly, none of the tested samples showed cytotoxic activity against normal cells; highlighting their good selectivity toward pathogenic bacteria and yeasts. Hence, they are promising lead candidates with antibacterial potential against methicillin resistant S. aureus (MRSA).

Apparel Design Scholarship Practices: Analysis of ITAA Professionals’ Design Abstract Proceedings From 1999 to 2017

2020 ◽  
pp. 0887302X2092146
Author(s):  
Young-A Lee ◽  
Seoha Min ◽  
Sumin Helen Koo
Keyword(s):  
Content Analysis ◽  
The Body ◽  
Apparel Design ◽  
Design Work ◽  
The Past ◽  
Body Of Knowledge ◽  
Textile And Apparel ◽  
Sustainability Practices ◽  
Citation Practices ◽  
The Impact

We explored the topical trends of the International Textile and Apparel Association professionals’ Design Abstract Proceedings (DAP) and how apparel design scholarship has been cited in the discipline for the past two decades. Using a content analysis, three research objectives were as follows: to examine (a) designer-identified keywords trends of the DAP, (b) to examine DAP directly cited in scholarly works, and (c) to examine DAP not directly cited but related to designers’ scholarship. Six overarching themes (inspirational references, apparel design, technology, sustainability practices, textiles, and nonapparel) were identified through the keywords analysis and used for further analyses. We found that design scholars were not used to cite other relevant scholarly works or their own works in their scholarly design work. The study findings provide an awareness for the strong need to establish citation practices for design scholars, which will add to the body of knowledge in clothing and textiles and increase the impact of design scholarship beyond the discipline.

International Mediation in Africa: Experiences and Challenges

2017 ◽  
Vol 22 (3) ◽  
pp. 402-430
Author(s):  
Vasu Gounden
Keyword(s):  
Mediation Process ◽  
The Past ◽  
Body Of Knowledge ◽  
International Mediation ◽  
Republic Of The Congo ◽  
Mediation Processes ◽  
The Cold War ◽  
The Impact ◽  
Deep Body

AbstractAlthough informal and traditionally driven practices of mediation have existed for many generations, institutionalized and African-driven mediation became more important following the end of the Cold War. Mediation initiatives undertaken over the past 25 years, partly as a consequence of the increase in intra-state conflicts on the continent, have resulted in the generation of a deep body of knowledge and the evolution of a community of practitioners. This article examines two of the first post-1990 African-driven mediation processes – the Arusha Peace Process for Burundi and the Inter-Congolese Dialogue (icd) for the Democratic Republic of the Congo (drc) – to highlight key lessons that emerged, including the choice of mediator, who to include in the mediation, the impact of regional and international dynamics on the mediation, the importance and challenges of addressing the root causes of the conflict in a mediation process, and the role of non-state actors and Track ii diplomacy.

Klebsiella pneumoniae in Germany: An overview on spatiotemporal distribution and resistance development in humans

2021 ◽  
Vol 1 (1) ◽  
pp. 16-25
Keyword(s):  
Klebsiella Pneumoniae ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistance Development ◽  
Federal States ◽  
Treatment Regimens ◽  
The Past ◽  
Resistance Patterns ◽  
Chronological Sequence ◽  
Rapid Dissemination

The emerging of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) is increasing worldwide. Rapid dissemination and increase of its incidence in Germany are observed and becoming a significant challenge for clinical laboratories and physicians. The current review highlights its chronological sequence of appearance and resistance development in humans in the past two decades in Germany. Emerging resistance problems of K. pneumoniae to the vast majority of available antimicrobial agents, including carbapenems and those of the ß-lactam group, were observed since the end of the last century and strains carrying diverse resistance patterns have emerged in most federal states of Germany. Still, several aspects of resistance development and pathogenesis are not fully understood. To date, hypervirulent K. pneumoniae (hvKp) isolates have been rarely isolated from German patients. The most frequent resistance genes identified are blaOXA-48, blaCTX-M-15, blaKPC-2, blaOXA-9, blaSHV-11, blaSHV-5 blaCTX-M-3, blaCTX-M-14, blaVIM-1 and the plasmid-encoded quinolone resistance (PMQR) gene. One Health genomic surveillance of K. pneumoniae strains from different reservoirs is required. This would help to understand in great detail the mechanisms leading to resistance development, spread and transmission, and developing alternative treatment regimens

Antimicrobial stewardship in wound care

2020 ◽  
Vol 29 (15) ◽  
pp. S10-S16
Author(s):  
Val Edwards-Jones
Keyword(s):  
Antimicrobial Stewardship ◽  
Antimicrobial Agents ◽  
Wound Care ◽  
Advisory Committees ◽  
Healthcare Facilities ◽  
Full Compliance ◽  
National Guidance ◽  
New Antibiotics ◽  
Underlying Causes ◽  
The Impact

Strategies to tackle the global crisis of antimicrobial resistance include implementing antimicrobial stewardship across the healthcare and agricultural sectors. Many clinical specialities have developed policies to advise practitioners on how to prescribe antibiotics more effectively, but there is still a lack of data on the impact of this change. Overuse and misuse of antibiotics have been commonplace since their introduction 70 years ago, and have contributed to the development of the resistance seen today. There is a dearth of new antibiotics and, if nothing is done to restrict the use of those that remain effective, there is a risk of returning to the pre-antibiotic era where simple infections could result in death. In wound care, it is essential that antibiotic treatment is appropriate to reduce infections. Many medical conditions predispose people to wounds that are difficult to heal and become chronic unless the underlying causes are addressed. Most wound infections are caused by bacteria, which are becoming increasingly resistant to commonly used antibiotics. This necessitates strict regimens for managing infection, which include prescribing antibiotics only when they are essential. Antimicrobial stewardship is undertaken in all UK healthcare facilities, and local advisory committees oversee the prudent use of antibiotics and other antimicrobial agents to try to prevent further increases in resistance. National guidance has been produced but whether full compliance has been followed has yet to be established and the impact of implementation needs to be analysed.

scholarly journals Protein Binding: Do We Ever Learn?

2011 ◽  
Vol 55 (7) ◽  
pp. 3067-3074 ◽  
Author(s):  
Markus A. Zeitlinger ◽  
Hartmut Derendorf ◽  
Johan W. Mouton ◽  
Otto Cars ◽  
William A. Craig ◽  
...  
Keyword(s):  
Protein Binding ◽  
Protein Concentration ◽  
Antimicrobial Agents ◽  
Quantitative Relationship ◽  
New Antibiotics ◽  
Protein Rich ◽  
High Degree ◽  
The Impact

ABSTRACTAlthough the influence of protein binding (PB) on antibacterial activity has been reported for many antibiotics and over many years, there is currently no standardization for pharmacodynamic models that account for the impact of protein binding of antimicrobial agentsin vitro. This might explain the somewhat contradictory results obtained from different studies. Simplein vitromodels which compare the MIC obtained in protein-free standard medium versus a protein-rich medium are prone to methodological pitfalls and may lead to flawed conclusions. Withinin vitrotest systems, a range of test conditions, including source of protein, concentration of the tested antibiotic, temperature, pH, electrolytes, and supplements may influence the impact of protein binding. As new antibiotics with a high degree of protein binding are in clinical development, attention and action directed toward the optimization and standardization of testing the impact of protein binding on the activity of antibioticsin vitrobecome even more urgent. In addition, the quantitative relationship between the effects of protein bindingin vitroandin vivoneeds to be established, since the physiological conditions differ. General recommendations for testing the impact of protein bindingin vitroare suggested.

scholarly journals New high-dose amoxicillin with clavulanate in therapy of acute respiratory and ENT infections in children

2021 ◽  
Vol 2 (1) ◽  
pp. 12-16
Author(s):  
Evelina E. Lokshina ◽  
Keyword(s):  
Risk Factors ◽  
Respiratory Tract Infections ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
High Dose ◽  
Drug Resistant ◽  
The Past ◽  
Disease Therapy ◽  
The Russian Federation ◽  
Tract Infections

A significant growth of bacterial resistance to antimicrobial agents has been reported globally over the past decades. Pneumococcus and Haemophilus influenzae are the major respiratory and ENT pathogens among children in the Russian Federation. To date, the problem of rational and effective bacterial respiratory tract infections therapy remains unsettled. The emergence of the new high-dose amoxicillin with clavulanate provides additional opportunities for respiratory disease therapy in children with risk factors for drug-resistant pathogens.

Antibiotic Resistance: What Is the Impact of Agricultural Uses of Antibiotics on Children’s Health?

PEDIATRICS ◽  
2003 ◽  
Vol 112 (Supplement_1) ◽  
pp. 253-258
Author(s):  
Katherine M. Shea
Keyword(s):  
Large Scale ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Human Medicine ◽  
Resistant Bacteria ◽  
Review Of The Literature ◽  
The Past ◽  
New Drug Development ◽  
The Impact ◽  
Lines Of Evidence

Antimicrobial resistance has reached crisis stage in human medicine. The rapid acceleration of multidrug-resistant bacteria in the past 2 decades has overtaken new drug development, and patients and clinicians are faced with the prospect of untreatable infections. Although much of the problem stems from overuse and misuse of antimicrobial agents in human medicine, large-scale use of antimicrobials in agriculture also contributes to the crisis. Agricultural uses of antibiotics produce environmental exposures in a variety of reservoirs, which select for resistant microbes and microbial genes. This article presents the major lines of evidence documenting the risks to human health of some of the agricultural uses of antimicrobials. A brief review of the microbiologic antecedents of resistance is followed by a discussion of agricultural uses of antimicrobials and a targeted review of the literature, which provides the background knowledge and evidence necessary for pediatricians and other clinicians to be informed and to advocate for judicious use of antimicrobials in all sectors.

Efficacy of Usnea sp. Extracts in Preventing Biofilm Formation by Bacillus Species Isolated from Soaking Liquor Samples

2020 ◽  
Vol 115 (6) ◽  
pp. 222-229
Author(s):  
Didem Berber ◽  
İpek Türkmenoğlu ◽  
Meral Birbir ◽  
Nüzhet Cenk Sesal
Keyword(s):  
Biofilm Formation ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Bacillus Species ◽  
Bacterial Biofilms ◽  
Bacterial Cells ◽  
Leather Industry ◽  
Acetone Extracts

Bacteria forms biofilm to be resistant to antibacterial agents and other unfavorable environment as compared to planktonic bacterial cells. Due to resistance of bacterial biofilms to commonly used antimicrobial agents and adverse effects of these biofilms in different industries, potential natural compounds which can inhibit bacterial biofilms have attracted more attention in recent years. Lichens are known to have unique secondary metabolites with various biological activities including anti-biofilm properties. Therefore, Bacillus toyonensis, Bacillus mojavensis, Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus cereus, and Bacillus licheniformis, isolated from soak liquor samples in the previous study, were tested for their ability to form biofilm in this study. Biofilm-forming Bacillus species were detected as B. subtilis, B. amyloliquefaciens, and B. velezensis. The anti-biofilm effect of the acetone extracts of Usnea sp. was evaluated at various concentrations against these biofilm-forming isolates. The anti-biofilm effect of acetone extracts of Usnea sp. against B. subtilis and B. amyloliquefaciens was observed at the concentration of 5 µg/mL by inhibition ratios of 62.75% and 72.72%, respectively. In addition, biofilm formation of B. velezensis was inhibited by the treatment with 1.25 µg/mL extracts at a 62.69% inhibition rate. Biofilm formations of B. amyloliquefaciens and B. velezensis were also suppressed by the extracts at varying percentages of inhibition ranging between 10.11-43.69% and 21.25-46.35%, respectively. This study may provide an alternative approach to overcome the biofilm formation and bacterial resistance to the antibacterial agents in the leather industry.

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