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Bacterial multidrug resistance problem solved by a broad-spectrum synthetic antibiotic

Posted in Advanced Drug Manufacturing Technology, Antibiotic resistance, Bacterial Resistance, Biochemical pathways, Cell Biology, Cell Biology, Signaling & Cell Circuits, Disease Biology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Carrier Design, Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, Drug Toxicity, Infectious Disease & New Antibiotic Targets, Microbiology, Molecular Genetics & Pharmaceutical, New Drug Approval, Pharmaceutical Drug Discovery, Population Health Management, Genetics & Pharmaceutical, Prescription Drugs Costs, Small Molecules in Development of Therapeutic Drugs, tagged Antibiotic resistance, antibiotics, antimicrobial resistance, bacteria, drug resistance, synthetic on March 1, 2023| Leave a Comment »

Bacterial multidrug resistance problem solved by a broad-spectrum synthetic antibiotic

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

There is an increasing demand for new antibiotics that effectively treat patients with refractory bacteremia, do not evoke bacterial resistance, and can be readily modified to address current and anticipated patient needs. Recently scientists described a promising compound of COE (conjugated oligo electrolytes) family, COE2-2hexyl, that exhibited broad-spectrum antibacterial activity. COE2-2hexyl effectively-treated mice infected with bacteria derived from sepsis patients with refractory bacteremia, including a CRE K. pneumoniae strain resistant to nearly all clinical antibiotics tested. Notably, this lead compound did not evoke drug resistance in several pathogens tested. COE2-2hexyl has specific effects on multiple membrane-associated functions (e.g., septation, motility, ATP synthesis, respiration, membrane permeability to small molecules) that may act together to abrogate bacterial cell viability and the evolution of drug-resistance. Impeding these bacterial properties may occur through alteration of vital protein–protein or protein-lipid membrane interfaces – a mechanism of action distinct from many membrane disrupting antimicrobials or detergents that destabilize membranes to induce bacterial cell lysis. The diversity and ease of COE design and chemical synthesis have the potential to establish a new standard for drug design and personalized antibiotic treatment.

Recent studies have shown that small molecules can preferentially target bacterial membranes due to significant differences in lipid composition, presence of a cell wall, and the absence of cholesterol. The inner membranes of Gram-negative bacteria are generally more negatively charged at their surface because they contain more anionic lipids such as cardiolipin and phosphatidylglycerol within their outer leaflet compared to mammalian membranes. In contrast, membranes of mammalian cells are largely composed of more-neutral phospholipids, sphingomyelins, as well as cholesterol, which affords membrane rigidity and ability to withstand mechanical stresses; and may stabilize the membrane against structural damage to membrane-disrupting agents such as COEs. Consistent with these studies, COE2-2hexyl was well tolerated in mice, suggesting that COEs are not intrinsically toxic in vivo, which is often a primary concern with membrane-targeting antibiotics. The COE refinement workflow potentially accelerates lead compound optimization by more rapid screening of novel compounds for the iterative directed-design process. It also reduces the time and cost of subsequent biophysical characterization, medicinal chemistry and bioassays, ultimately facilitating the discovery of novel compounds with improved pharmacological properties.

Additionally, COEs provide an approach to gain new insights into microbial physiology, including membrane structure/function and mechanism of drug action/resistance, while also generating a suite of tools that enable the modulation of bacterial and mammalian membranes for scientific or manufacturing uses. Notably, further COE safety and efficacy studies are required to be conducted on a larger scale to ensure adequate understanding of the clinical benefits and risks to assure clinical efficacy and toxicity before COEs can be added to the therapeutic armamentarium. Despite these limitations, the ease of molecular design, synthesis and modular nature of COEs offer many advantages over conventional antimicrobials, making synthesis simple, scalable and affordable. It enables the construction of a spectrum of compounds with the potential for development as a new versatile therapy for the emergence and rapid global spread of pathogens that are resistant to all, or nearly all, existing antimicrobial medicines.

References:

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(23)00026-9/fulltext#%20

https://pubmed.ncbi.nlm.nih.gov/36801104/

https://www.sciencedaily.com/releases/2023/02/230216161214.htm

https://www.nature.com/articles/s41586-021-04045-6

https://www.nature.com/articles/d43747-020-00804-y

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Non-toxic antiviral nanoparticles with a broad spectrum of virus inhibition

Posted in Allergy and Infectious Diseases, Antibiotic resistance, Cell Biology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Enzyme Induction, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Nanotechnology for Drug Delivery, Oligonucleotide Therapeutics & Delivery, Small Molecules in Development of Therapeutic Drugs, Vaccinology, Viral diseases, virology, Virology - Vector-borne DIsease, tagged antiviral drugs, Computer Model, Dengue, Ebola virus, gold nanoparticles, HIV, human papillomavirus hpv, Infectious Diseases, Influenza, nanotechnology, viral capsid on June 20, 2021| Leave a Comment »

Non-toxic antiviral nanoparticles with a broad spectrum of virus inhibition

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Infectious diseases account for 20% of global deaths, with viruses accounting for over a third of these deaths (1). Lower respiratory effects and human immunodeficiency viruses (HIV) are among the top ten causes of death worldwide, both of which contribute significantly to health-care costs (2). Every year, new viruses (such as Ebola) increase the mortality toll. Vaccinations are the most effective method of avoiding viral infections, but there are only a few of them, and they are not available in all parts of the world (3). After infection, antiviral medications are the only option; unfortunately, only a limited number of antiviral medications are approved in this condition. Antiviral drugs on a big scale that can influence a wide spectrum of existing and emerging viruses are critical.

The three types of treatments currently available are small molecules (such as nucleoside analogues and peptidomimetics), proteins that stimulate the immune system (such as interferon), and oligonucleotides (for example, fomivirsen). The primary priorities include HIV, hepatitis B and C viruses, Herpes Simplex Virus (HSV), human cytomegalovirus (HCMV), and influenza virus. They work mainly on viral enzymes, which are necessary for viral replication but which differ from other host enzymes to ensure selective function. The specificity of antivirals is far from perfect because viruses rely on the biosynthesis machinery for reproduction of infected cells, which results in a widespread and inherent toxicity associated with such therapy. However, most viruses mutate rapidly due to their improper replicating mechanisms and so often develop resistance (4). Finally, since antiviral substances are targeted at viral proteins, it is challenging to build broad-based antivirals that can act with a wide range of phylogenetic and structurally different virus.

Over the last decade breakthroughs in nanotechnology have led to scientists developing incredibly specialized nanoparticles capable of traveling in specific cells through a human body. A broad spectrum of destructive viruses is being targeted and not only bind to, but also destroy, by modern computer modeling technology.

An international team of researchers led by the University of Illinois at Chicago chemistry professor Petr Kral developed novel anti-viral nanoparticles that bind to a variety of viruses, including herpes simplex virus, human papillomavirus, respiratory syncytial virus, Dengue, and lentiviruses. In contrast to conventional broad-spectrum antivirals, which just prevent viruses from invading cells, the new nanoparticles eradicate viruses. The team’s findings have been published in the journal “Nature Materials.”

A molecular dynamics model showing a nanoparticle binding to the outer envelope of the human papillomavirus. (Credit: Petr Kral) https://today.uic.edu/files/2017/09/viralbindingcropped.png

The goal of this new study was to create a new anti-viral nanoparticle that could exploit the HSPG binding process to not only tightly attach with virus particles but also to destroy them. The work was done by a group of researchers ranging from biochemists to computer modeling experts until the team came up with a successful nanoparticle design that could, in principle, accurately target and kill individual virus particles.

The first step to combat many viruses consists in the attachment of heparin sulfate proteoglycan on cell surfaces to a protein (HSPG). Some of the antiviral medications already in place prevent an infection by imitating HSPG’s connection to the virus. An important constraint of these antivirals is that not only is this antiviral interaction weak, it does not kill the virus.

Kral said

We knew how the nanoparticles should bind on the overall composition of HSPG binding viral domains and the structures of the nanoparticles, but we did not realize why the various nanoparticles act so differently in terms of their both bond strength and viral entry in cells

Kral and colleagues assisted in resolving these challenges and guiding the experimentalists in fine-tuning the nanoparticle design so that it performed better.

The researchers have employed advanced computer modeling techniques to build exact structures of several target viruses and nanoparticles up to the atom’s position. A profound grasp of the interactions between individual atom groupings in viruses and nanoparticles allows the scientists to evaluate the strength and duration of prospective links between these two entities and to forecast how the bond could change over time and eventually kill the virus.

Atomistic MD simulations of an L1 pentamer of HPV capsid protein with the small NP (2.4 nm core, 100 MUP ligands). The NP and the protein are shown by van der Waals (vdW) and ribbon representations respectively. In the protein, the HSPG binding amino acids are displayed by vdW representation.

Kral added

We were capable of providing the design team with the data needed to construct a prototype of an antiviral of high efficiency and security, which may be utilized to save lives

The team has conducted several in vitro experiments following the development of a prototype nanoparticle design which have demonstrated success in binding and eventually destroying a wide spectrum of viruses, including herpes simplex, human papillomaviruses, respiratory syncytial viruses and dengue and lentiviruses.

The research is still in its early phases, and further in vivo animal testing is needed to confirm the nanoparticles’ safety, but this is a promising new road toward efficient antiviral therapies that could save millions of people from devastating virus infections each year.

The National Centers of Competence in Research on Bio-Inspired Materials, the University of Turin, the Ministry of Education, Youth and Sports of the Czech Republic, the Leenards Foundation, National Science Foundation award DMR-1506886, and funding from the University of Texas at El Paso all contributed to this study.

Main Source

Cagno, V., Andreozzi, P., D’Alicarnasso, M., Silva, P. J., Mueller, M., Galloux, M., … & Stellacci, F. (2018). Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism. Nature materials, 17(2), 195-203. https://www.nature.com/articles/nmat5053

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Rare earth-doped nanoparticles applications in biological imaging and tumor treatment

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2020/10/04/rare-earth-doped-nanoparticles-applications-in-biological-imaging-and-tumor-treatment/

Nanoparticles Could Boost Effectiveness of Allergy Shots

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2019/05/25/nanoparticles-could-boost-effectiveness-of-allergy-shots/

Immunoreactivity of Nanoparticles

Author: Tilda Barliya PhD

https://pharmaceuticalintelligence.com/2012/10/27/immunoreactivity-of-nanoparticles/

Nanotechnology and HIV/AIDS Treatment

Author: Tilda Barliya, PhD

https://pharmaceuticalintelligence.com/2012/12/25/nanotechnology-and-hivaids-treatment/

Nanosensors for Protein Recognition, and gene-proteome interaction

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/01/30/nanosensors-for-protein-recognition-and-gene-proteome-interaction/

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The Journey of Antibiotic Discovery

Posted in Allergy and Infectious Diseases, Antibiotic resistance, Artificial Intelligence Applications in Health Care, Artificial Intelligence in Health Care - Tools & Innovations, Biological Networks, Electronic Health Record, Genomics Pharmacy, Health Care System by Country, Health Economics and Outcomes Research, Health Law & Patient Safety, Healthcare Reform, Human Immune System in Health and in Disease, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Metabolomics, Microbiologial genetics, Microbiology, microbiome, Nutrigenomics, Personal Health Applications: Tech Innovations serves HealhCare, Pharmacogenomics, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Proteomics, tagged anti, antibiotic discovery platforms, Antibiotic resistance, antibiotics, Infectious disease, therapeutics on May 19, 2019| Leave a Comment »

The Journey of Antibiotic Discovery

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

The term ‘antibiotic’ was introduced by Selman Waksman as any small molecule, produced by a microbe, with antagonistic properties on the growth of other microbes. An antibiotic interferes with bacterial survival via a specific mode of action but more importantly, at therapeutic concentrations, it is sufficiently potent to be effective against infection and simultaneously presents minimal toxicity. Infectious diseases have been a challenge throughout the ages. From 1347 to 1350, approximately one-third of Europe’s population perished to Bubonic plague. Advances in sanitary and hygienic conditions sufficed to control further plague outbreaks. However, these persisted as a recurrent public health issue. Likewise, infectious diseases in general remained the leading cause of death up to the early 1900s. The mortality rate shrunk after the commercialization of antibiotics, which given their impact on the fate of mankind, were regarded as a ‘medical miracle’. Moreover, the non-therapeutic application of antibiotics has also greatly affected humanity, for instance those used as livestock growth promoters to increase food production after World War II.

Currently, more than 2 million North Americans acquire infections associated with antibiotic resistance every year, resulting in 23,000 deaths. In Europe, nearly 700 thousand cases of antibiotic-resistant infections directly develop into over 33,000 deaths yearly, with an estimated cost over €1.5 billion. Despite a 36% increase in human use of antibiotics from 2000 to 2010, approximately 20% of deaths worldwide are related to infectious diseases today. Future perspectives are no brighter, for instance, a government commissioned study in the United Kingdom estimated 10 million deaths per year from antibiotic resistant infections by 2050.

The increase in antibiotic-resistant bacteria, alongside the alarmingly low rate of newly approved antibiotics for clinical usage, we are on the verge of not having effective treatments for many common infectious diseases. Historically, antibiotic discovery has been crucial in outpacing resistance and success is closely related to systematic procedures – platforms – that have catalyzed the antibiotic golden age, namely the Waksman platform, followed by the platforms of semi-synthesis and fully synthetic antibiotics. Said platforms resulted in the major antibiotic classes: aminoglycosides, amphenicols, ansamycins, beta-lactams, lipopeptides, diaminopyrimidines, fosfomycins, imidazoles, macrolides, oxazolidinones, streptogramins, polymyxins, sulphonamides, glycopeptides, quinolones and tetracyclines.

The increase in drug-resistant pathogens is a consequence of multiple factors, including but not limited to high rates of antimicrobial prescriptions, antibiotic mismanagement in the form of self-medication or interruption of therapy, and large-scale antibiotic use as growth promotors in livestock farming. For example, 60% of the antibiotics sold to the USA food industry are also used as therapeutics in humans. To further complicate matters, it is estimated that $200 million is required for a molecule to reach commercialization, with the risk of antimicrobial resistance rapidly developing, crippling its clinical application, or on the opposing end, a new antibiotic might be so effective it is only used as a last resort therapeutic, thus not widely commercialized.

Besides a more efficient management of antibiotic use, there is a pressing need for new platforms capable of consistently and efficiently delivering new lead substances, which should attend their precursors impressively low rates of success, in today’s increasing drug resistance scenario. Antibiotic Discovery Platforms are aiming to screen large libraries, for instance the reservoir of untapped natural products, which is likely the next antibiotic ‘gold mine’. There is a void between phenotanypic screening (high-throughput) and omics-centered assays (high-information), where some mechanistic and molecular information complements antimicrobial activity, without the laborious and extensive application of various omics assays. The increasing need for antibiotics drives the relentless and continuous research on the foreground of antibiotic discovery. This is likely to expand our knowledge on the biological events underlying infectious diseases and, hopefully, result in better therapeutics that can swing the war on infectious diseases back in our favor.

During the genomics era came the target-based platform, mostly considered a failure due to limitations in translating drugs to the clinic. Therefore, cell-based platforms were re-instituted, and are still of the utmost importance in the fight against infectious diseases. Although the antibiotic pipeline is still lackluster, especially of new classes and novel mechanisms of action, in the post-genomic era, there is an increasingly large set of information available on microbial metabolism. The translation of such knowledge into novel platforms will hopefully result in the discovery of new and better therapeutics, which can sway the war on infectious diseases back in our favor.

References:

https://www.mdpi.com/2079-6382/8/2/45/htm

https://www.ncbi.nlm.nih.gov/pubmed/19515346

https://www.ajicjournal.org/article/S0196-6553(11)00184-2/fulltext

https://www.ncbi.nlm.nih.gov/pubmed/21700626

http://www.med.or.jp/english/journal/pdf/2009_02/103_108.pdf

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NEW Book #InfectiousDiseases #Immunology #stresssignaling #Therapeutics check https://www.amazon.com/dp/B075CXHY1B

Posted in Antibiotic resistance, Immunodiagnostics, Immunology, Immunotherapy, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, LPBI Group, e-Scientific Media, DFP, R&D-M3DP, R&D-Drug Discovery, US Patents: SOPs and Team Management, Viral diseases on November 9, 2017| Leave a Comment »

NEW Book #InfectiousDiseases #Immunology #StressSignaling #Therapeutics check https://www.amazon.com/dp/B075CXHY1B

Editor-in-Chief: Aviva Lev-Ari, PhD, RN

Includes FDA Approved Drugs for Infections and Infectious Diseases: Bacterial Infection, Viral Infection, Fungal Infection, Allergy-related Infections and Other, 1995 – 2016

VOLUME 2: covers the frontier of research on Infectious Diseases and the Human Immune System. The Immune Response, Disease Specific Immune Response, Immunodiagnostics and Immunotherapy, Immunotherapy and Autoimmunity,
Bacterial Infections, Bacteria Types, Antibactirial Therapeutics, FDA Approved Drugs for Infections and Infectious Diseases: Bacterial Infection, 1995 – 2016. Viral Infection: Virus Types, Antiviral Therapeutics, and FDA Approved Drugs for Infections and Infectious Diseases: Viral Infection, Fungal Infections, Allergy-related Infections, Other Infections,1995 – 2016,

VOLUME 3: covers the state of Science on the Historical Perspective of Immunology, Development of the Immune System, Signaling and Immunology, Cellular Immunity, Immunology and Inflammatory Response. Antibody-based Immunity, Vaccines and Microbiome, Immuno-Pharmaceutics, Cancer Immunotherapy, Immunomodulation and Neuro-Immunology.

Volume 2: Summary
The material that has been covered is a considerable material on the basic types of infections – bacterial, viral, and fungal, and diseases related to immune mechanisms. There has been a substantial coverage of the drugs and the manufacturers. This material brings to the discussion an international problem of drug resistance that applies much to bacteria, and a considerable amount of material on advances in drug development that takes into consideration protein structure and protein-protein interactions. The coverage of virus diseases brings to the forefront vaccines. However, in such cases as the influenza virus, a rapid genetic change of the virus makes the use of vaccines an issue for continuing revision.

Volume 3: Summary
The second volume is only concerned with the pathobiology of the inflammatory response, including sepsis, and it does not leave out hematopoiesis, and it lays out the difference between the B-clles and the T-cells that are related to the Toll receptor. Here we have looked closely at two immune disorders, Inflammatory Bowel Disease (Crohn’s Disease) and Rheumatoid Arthritis. Here we have discussed immunomodulation and signaling of the pathways involved, and the programmed cell death response. We have also covered the relationship of the immune response to autoimmune disorders and to cancer. The treatment of cancer now heavily leans toward the blocking of destructive processes in the immunomodulatory pathways.

Epilogue – Volume 2
Volume 2 has covered the most common bacterial and viral diseases that we find widely, or sporadically. It detailed the development of sepsis, and the immune response factor. The immune response involves local cellular invasion of lymphocytes related to initiation of T-cells and macrophages, and also the proteomic generated B-cell antibodies. These reactions are both local and systemic, as bacterial invasion is local and usually related to the tissue of residence (large intestine, oral, lung, genital). In the case of virus, the site of entry is often respiratory or by food intake, but these agents may rapidly become systemic. The other matter of the immune response is autoimmune, a reaction against the self. It is not entirely clear how this is initiated, but it has been related to failure to develop immunity in the prenatal or postnatal period. The only other possibility that might be considered would be by the mechanism of cell remodeling by an apoptotic related mechanism. The other chapters deal with therapeutics.

Epilogue – Volume 3
These two volumes have traversed a large knowledge-base. The first was directed largely at the well known bacterial, virus, fungal diseases, as well as autoimmunity. It specified recent FDA approved recommendations of pharmaceutics for these conditions. It also gives some attention to the immune response in inflammatory and autoimmune diseases, but not cancer. The second volume gives a concise history of development of Leukemias, Lymphomas pathology.

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NOW on Amazon.com our 10th e-Book: https://www.amazon.com/dp/B075CXHY1B The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: Volume 2 & 3

Posted in Antibiotic resistance, CANCER BIOLOGY & Innovations in Cancer Therapy, Immuno-Oncology & Genomics, Immunodiagnostics, Immunotherapy, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Innovation in Immunology Diagnostics, Viral diseases, Virology - Vector-borne DIsease on September 5, 2017| Leave a Comment »

Announcing our 10th e-Book on Amazon.com – 1st day, 9/4/2017

Editor-in-Chief: Aviva Lev-Ari, PhD, RN

On our Book Shelf on Amazon.com

WE ARE ON AMAZON.COM

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The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: VOLUME 2: Infectious Diseases and Therapeutics and VOLUME 3: The Immune System and Therapeutics (Series D: BioMedicine & Immunology) Kindle Edition – on Amazon.com since 9/4/2017

by Larry H. Bernstein (Author), Aviva Lev-Ari (Author), Stephen J. Williams (Author), Demet Sag (Author), Irina Robu (Author), Tilda Barliya (Author), David Orchard-Webb (Author), Alan F. Kaul (Author), Danut Dragoi (Author), Sudipta Saha (Editor)

https://www.amazon.com/dp/B075CXHY1B

Product details

File Size:21832 KB
Print Length:3747 pages
Publisher:Leaders in Pharmaceutical Business Intelligence (LPBI) Group; 1 edition (September 4, 2017)
Publication Date:September 4, 2017
Sold by:Amazon Digital Services LLC
Language:English
ASIN:B075CXHY1B
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How to distinguish between viral, bacterial infections: New Tool developed @University of Rochester Medical Center

Posted in Antibiotic resistance, Diagnostics and Lab Tests, Disease Biology, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Transcriptomics, Viral diseases, Virology - Vector-borne DIsease, tagged Lower respiratory tract infection (LRTI) on August 2, 2017| Leave a Comment »

Curator: Aviva Lev-Ari, PhD, RN

Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness

Scientific Reports 7, Article number: 6548(2017)
doi:10.1038/s41598-017-06738-3
Download Citation
- Molecular biology
- Molecular medicine

Published online: 26 July 2017

URMC Researchers Developing New Tool to Fight Antibiotic Resistance

Goal is to Distinguish Between Viral and Bacterial Infections, Reduce Unnecessary Use of Antibiotics

Friday, July 28, 2017

“It’s extremely difficult to interpret what’s causing a respiratory tract infection, especially in very ill patients who come to the hospital with a high fever, cough, shortness of breath and other concerning symptoms,” said Ann R. Falsey, M.D., lead study author, professor and interim chief of the Infectious Diseases Division at UR Medicine’s Strong Memorial Hospital.

“My goal is to develop a tool that physicians can use to rule out a bacterial infection with enough certainty that they are comfortable, and their patients are comfortable, foregoing an antibiotic.”

Ann R. Falsey, M.D.

Falsey’s project caught the attention of the federal government; she’s one of 10 semifinalists in the Antimicrobial Resistance Diagnostic Challenge, a competition sponsored by NIH and the Biomedical Advanced Research and Development Authority to help combat the development and spread of drug resistant bacteria. Selected from among 74 submissions, Falsey received $50,000 to continue her research and develop a prototype diagnostic test, such as a blood test, using the genetic markers her team identified.

SOURCE

https://www.urmc.rochester.edu/news/story/5108/urmc-researchers-developing-new-tool-to-fight-antibiotic-resistance.aspx

Lower respiratory tract infection (LRTI)

We enrolled 94 subjects who were microbiologically classified; 53 as “non-bacterial” and 41 as “bacterial”. RNAseq and qPCR confirmed significant differences in mean expression for 10 genes previously identified as discriminatory for bacterial LRTI. A novel dimension reduction strategy selected three pathways (lymphocyte, α-linoleic acid metabolism, IGF regulation) including eleven genes as optimal markers for discriminating bacterial infection (naïve AUC = 0.94; nested CV-AUC = 0.86). Using these genes, we constructed a classifier for bacterial LRTI with 90% (79% CV) sensitivity and 83% (76% CV) specificity. This novel, pathway-based gene set displays promise as a method to distinguish bacterial from nonbacterial LRTI.

https://www.nature.com/articles/s41598-017-06738-3#Sec8