scholarly journals Are Phage Lytic Proteins the Secret Weapon To Kill Staphylococcus aureus?

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Diana Gutiérrez ◽  
Lucía Fernández ◽  
Ana Rodríguez ◽  
Pilar García

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most threatening microorganisms for global human health. The current strategies to reduce the impact of S. aureus include a restrictive control of worldwide antibiotic use, prophylactic measures to hinder contamination, and the search for novel antimicrobials to treat human and animal infections caused by this bacterium. The last strategy is currently the focus of considerable research. In this regard, phage lytic proteins (endolysins and virion-associated peptidoglycan hydrolases [VAPGHs]) have been proposed as suitable candidates. Indeed, these proteins display narrow-spectrum antimicrobial activity and a virtual lack of bacterial-resistance development. Additionally, the therapeutic use of phage lytic proteins in S. aureus animal infection models is yielding promising results, showing good efficacy without apparent side effects. Nonetheless, human clinical trials are still in progress, and data are not available yet. This minireview also analyzes the main obstacles for introducing phage lytic proteins as human therapeutics against S. aureus infections. Besides the common technological problems derived from large-scale production of therapeutic proteins, a major setback is the lack of a proper legal framework regulating their use. In that sense, the relevant health authorities should urgently have a timely discussion about these new antimicrobials. On the other hand, the research community should provide data to dispel any doubts regarding their efficacy and safety. Overall, the appropriate scientific data and regulatory framework will encourage pharmaceutical companies to invest in these promising antimicrobials.

2021 ◽  
Vol 8 ◽  
Author(s):  
Maria de Fátima Brito ◽  
Carla Torre ◽  
Beatriz Silva-Lima

Diabetes Mellitus is one of the World Health Organization's priority diseases under research by the first and second programmes of Innovative Medicines Initiative, with the acronyms IMI1 and IMI2, respectively. Up to October of 2019, 13 projects were funded by IMI for Diabetes & Metabolic disorders, namely SUMMIT, IMIDIA, DIRECT, StemBANCC, EMIF, EBiSC, INNODIA, RHAPSODY, BEAT-DKD, LITMUS, Hypo-RESOLVE, IM2PACT, and CARDIATEAM. In general, a total of €447 249 438 was spent by IMI in the area of Diabetes. In order to prompt a better integration of achievements between the different projects, we perform a literature review and used three data sources, namely the official project's websites, the contact with the project's coordinators and co-coordinator, and the CORDIS database. From the 662 citations identified, 185 were included. The data collected were integrated into the objectives proposed for the four IMI2 program research axes: (1) target and biomarker identification, (2) innovative clinical trials paradigms, (3) innovative medicines, and (4) patient-tailored adherence programmes. The IMI funded projects identified new biomarkers, medical and research tools, determinants of inter-individual variability, relevant pathways, clinical trial designs, clinical endpoints, therapeutic targets and concepts, pharmacologic agents, large-scale production strategies, and patient-centered predictive models for diabetes and its complications. Taking into account the scientific data produced, we provided a joint vision with strategies for integrating personalized medicine into healthcare practice. The major limitations of this article were the large gap of data in the libraries on the official project websites and even the Cordis database was not complete and up to date.


2013 ◽  
Vol 57 (9) ◽  
pp. 4410-4416 ◽  
Author(s):  
Lidia Kardaś-Słoma ◽  
Pierre-Yves Boëlle ◽  
Lulla Opatowski ◽  
Didier Guillemot ◽  
Laura Temime

ABSTRACTInterventions designed to reduce antibiotic consumption are under way worldwide. While overall reductions are often achieved, their impact on the selection of antibiotic-resistant selection cannot be assessed accurately from currently available data. We developed a mathematical model of methicillin-sensitive and methicillin-resistantStaphylococcus aureus(MSSA and MRSA) transmission inside and outside the hospital. A systematic simulation study was then conducted with two objectives: to assess the impact of antibiotic class-specific changes during an antibiotic reduction period and to investigate the interactions between antibiotic prescription changes in the hospital and the community. The model reproduced the overall reduction in MRSA frequency in French intensive-care units (ICUs) with antibiotic consumption in France from 2002 to 2003 as an input. However, the change in MRSA frequency depended on which antibiotic classes changed the most, with the same overall 10% reduction in antibiotic use over 1 year leading to anywhere between a 69% decrease and a 52% increase in MRSA frequency in ICUs and anywhere between a 37% decrease and a 46% increase in the community. Furthermore, some combinations of antibiotic prescription changes in the hospital and the community could act in a synergistic or antagonistic way with regard to overall MRSA selection. This study shows that class-specific changes in antibiotic use, rather than overall reductions, need to be considered in order to properly anticipate the impact of an antibiotic reduction campaign. It also highlights the fact that optimal gains will be obtained by coordinating interventions in hospitals and in the community, since the effect of an intervention in a given setting may be strongly affected by exogenous factors.


2021 ◽  
Vol 17 (1) ◽  
pp. 107-113
Author(s):  
Chantal Mak

While private corporations have become increasingly influential in the global economy, a comprehensive legal framework for their activities is missing. Although international and regional legal instruments may govern some aspects of, for instance, international investments and the supply of goods and services, there is no overarching structure for assessing the impact of large-scale private projects. In the absence of such a comprehensive framework, specific rules of private law allow profit-seeking companies to expand their activities on an economic basis, mostly without having to heed social concerns (Pistor, 2019). This is particularly problematic insofar as multinational companies have obtained power to set the rules for their engagement with states, organisations and individuals, for instance in the form of transnational investment contracts. Given the fragmented nature of the legal sphere in which such contracts are elaborated and performed, those who face the harmful consequences of such investments may not be able to participate in decision-making processes. The contracts remain in ‘wild zones’ of globalisation (Fraser, 2014, p. 150), where powerful private companies rule.


Author(s):  
Franka Lestin-Bernstein ◽  
Ramona Harberg ◽  
Ingo Schumacher ◽  
Lutz Briedigkeit ◽  
Oliver Heese ◽  
...  

Abstract Background Antimicrobial stewardship (AMS) strategies worldwide focus on optimising the use of antibiotics. Selective susceptibility reporting is recommended as an effective AMS tool although there is a lack of representative studies investigating the impact of selective susceptibility reporting on antibiotic use. The aim of this study was to investigate the impact of selective susceptibility reporting of Staphylococcus aureus (S. aureus) on antibiotic consumption. Enhancing the use of narrow-spectrum beta-lactam antibiotics such as flucloxacillin/cefazolin/cefalexin is one of the main goals in optimising antibiotic therapy of S. aureus infections. Methods This interventional study with control group was conducted at a tertiary care hospital in Germany. During the one-year interventional period susceptibility reports for all methicillin-sensitive S. aureus (MSSA) were restricted to flucloxacillin/cefazolin/cefalexin, trimethoprim-sulfamethoxazole, clindamycin, gentamicin and rifampin/fosfomycin, instead of reporting all tested antibiotics. The impact of implementing selective reporting was analysed by monitoring total monthly antibiotic consumption in our hospital and in a reference hospital (recommended daily dose/100 occupied bed days: RDD/100 BD), as well as on an individual patient level by analysing days of therapy adjusted for bed days (DOT/ 100 BD) for patients with S. aureus bacteremia (SAB) and respectively skin and soft tissue infections (SSTI). Results MSSA-antibiograms were acquired for 2836 patients. The total use of narrow-spectrum beta-lactams more than doubled after implementing selective reporting (from 1.2 to 2.8 RDD/100 BD, P < 0.001). The use of intravenous flucloxacillin/cefazolin for SAB rose significantly from 52 to 75 DOT/100 BD (plus 42%), just as the use of oral cefalexin for SSTI (from 1.4 to 9.4 DOT/100 BD, from 3 to 17 of 85/88 patients). Considering the overall consumption, there was no decrease in antibiotics omitted from the antibiogram. This was probably due to their wide use for other infections. Conclusions As narrow-spectrum beta-lactams are not widely used for other infections, their increase in the overall consumption of the entire hospital was a strong indicator that selective reporting guided clinicians to an optimised antibiotic therapy of S. aureus infections. On a patient level, this assumption was verified by a significant improved treatment of S. aureus infections in the subgroups of SAB and SSTI. As useful AMS tool, we recommend implementing selective reporting rules into the national/international standards for susceptibility reporting.


2020 ◽  
Author(s):  
Franka Lestin-Bernstein ◽  
Ramona Harberg ◽  
Ingo Schumacher ◽  
Lutz Briedigkeit ◽  
Oliver Heese ◽  
...  

Abstract Background:Antimicrobial stewardship (AMS) strategies worldwide focus on optimised antibiotic use. Selective susceptibility reporting is recommended as an effective AMS tool, although there is a lack of representative studies investigating the impact of selective susceptibility reporting on antibiotic use.The aim of this study was to investigate the impact of selective susceptibility reporting of Staphylococcus aureus (S. aureus) on antibiotic consumption. Enhancing the use of narrow-spectrum beta-lactam antibiotics such as flucloxacillin/cefazolin/cefalexin is one of the main goals in optimising antibiotic therapy of S. aureus infections.Methods:This interventional study with control group was conducted at a tertiary care hospital in Germany. During the one-year interventional period, susceptibility reports for all methicillin-sensitive S. aureus (MSSA) were restricted to flucloxacillin/cefazolin/oral cefalexin, trimethoprim-sulfamethoxazole, clindamycin, gentamicin and rifampin/fosfomycin; instead of reporting all tested antibiotics during the year before the intervention and in the reference clinic. The impact of the intervention was analysed by monitoring antibiotic consumption (recommended daily dose/100 occupied bed days: RDD/100 BD).Results:MSSA-antibiograms were reported for 2836 patients. Total use of narrow-spectrum beta-lactams more than doubled during the intervention (from 1.2 to 2.8 RDD/100 BD, P<0.001; P<0.001 compared to the reference clinic); the percentage of total antibiotic use increased from 2.6% to 6.2%. A slight, but significant increase in the use of trimethoprim-sulfamethoxazole was also observed (+ 0.37 RDD/100 BD).There was no decrease in antibiotics withdrawn from the antibiogram, probably as a consequence of their wide use for indications other than S. aureus infections.Conclusions:As narrow-spectrum beta-lactams are not widely used for other infections, there is a strong indication that selective reporting guided clinicians to optimised antibiotic therapy of S. aureus infections.As useful AMS tool, we recommend implementing selective reporting rules into the national/international standards for susceptibility reporting.


Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 414
Author(s):  
Mary Garvey

Antimicrobial resistance necessitates action to reduce and eliminate infectious disease, ensure animal and human health, and combat emerging diseases. Species such as Acinetobacter baumanniii, vancomycin resistant Enterococcus, methicillin resistance Staphylococcus aureus, and Pseudomonas aeruginosa, as well as other WHO priority pathogens, are becoming extremely difficult to treat. In 2017, the EU adopted the “One Health” approach to combat antibiotic resistance in animal and human medicine and to prevent the transmission of zoonotic disease. As the current therapeutic agents become increasingly inadequate, there is a dire need to establish novel methods of treatment under this One Health Framework. Bacteriophages (phages), viruses infecting bacterial species, demonstrate clear antimicrobial activity against an array of resistant species, with high levels of specificity and potency. Bacteriophages play key roles in bacterial evolution and are essential components of all ecosystems, including the human microbiome. Factors such are their specificity, potency, biocompatibility, and bactericidal activity make them desirable options as therapeutics. Issues remain, however, relating to their large-scale production, formulation, stability, and bacterial resistance, limiting their implementation globally. Phages used in therapy must be virulent, purified, and well characterized before administration. Clinical studies are warranted to assess the in vivo pharmacokinetics and pharmacodynamic characteristics of phages to fully establish their therapeutic potential.


2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Glen P. Carter ◽  
Mark B. Schultz ◽  
Sarah L. Baines ◽  
Anders Gonçalves da Silva ◽  
Helen Heffernan ◽  
...  

ABSTRACTTopical antibiotics, such as mupirocin and fusidic acid, are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, the widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains. New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences single-molecule real-time (SMRT) whole-genome sequencing, Illumina short-read sequencing, and Bayesian phylogenomic modeling on 118 new multilocus sequence type 1 (ST1) communityStaphylococcus aureusisolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1S. aureus. We also providein vitroexperimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDRS. aureusisolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.


2020 ◽  
Author(s):  
Styliani Geronikolou ◽  
George Chrousos

UNSTRUCTURED The World Health Organization named the phenomenon of misinformation spread through the social media “infodemics”, and recognized the need to curb it. Misinformation infodemics undermine not only population safety, but also compliance to the suggestions/prophylactic measures recommended in pandemics. The aim of this study was to review the impact of social media on general population fear in “infoveillance” studies during the COVID-19 pandemic. PRISMA protocol was followed and six out of twenty studies were retrieved, meta-analyzed, and had their findings presented in the form of a Forest plot. The summary random and significant event rate was 0.298, 95% CI respectively 0.213 and 0.400, suggesting that social media-circulated misinformation related to COVID-19 triggered public fear and other manifestations. These findings merit special attention by public health authorities. Thus, “infodemiology” and Infoveillance are valid tools in the hands of epidemiologists to help prevent dissemination of false information, with potentially damaging effects.


Materials ◽  
2019 ◽  
Vol 12 (24) ◽  
pp. 4161 ◽  
Author(s):  
Vincenzo Tagliaferri ◽  
Federica Trovalusci ◽  
Stefano Guarino ◽  
Simone Venettacci

In this study, the authors present a comparative analysis of different additive manufacturing (AM) technologies for high-performance components. Four 3D printers, currently available on the Italian national manufacturing market and belonging to three different AM technologies, were considered. The analysis focused on technical aspects to highlight the characteristics and performance limits of each technology, economic aspects to allow for an assessment of the costs associated with the different processes, and environmental aspects to focus on the impact of the production cycles associated with these technologies on the ecosystem, resources and human health. This study highlighted the current limits of additive manufacturing technologies in terms of production capacity in the case of large-scale production of plastic components, especially large ones. At the same time, this study highlights how the geometry of the object to be developed greatly influences the optimal choice between the various AM technologies, in both technological and economic terms. Fused deposition modeling (FDM) is the technology that exhibits the greatest limitations hindering mass production due to production times and costs, but also due to the associated environmental impact.


2012 ◽  
Vol 13 (1) ◽  
pp. 50-63 ◽  
Author(s):  
Shan C. Sutton

Introduction Few writings within the realms of archives and special collections have reverberated throughout the field to the degree of Mark A. Greene and Dennis Meissner’s 2005 article “More Product, Less Process: Revamping Traditional Archival Processing.”1 Its clarion call to shift archival arrangement and description away from time-consuming, detailed processes toward rapid, minimalist strategies was met with both cheers and groans that continue unabated. In a sign of its ubiquity, the approach advocated by Greene and Meissner is now simply referred to as “MPLP,” and its implementation is the subject of ongoing discussion in numerous venues, including professional journals, conference . . .


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