scholarly journals Bacteriophage Therapy of Bacterial Infections: The Rediscovered Frontier

2021 ◽  
Vol 14 (1) ◽  
pp. 34
Author(s):  
Nejat Düzgüneş ◽  
Melike Sessevmez ◽  
Metin Yildirim
Keyword(s):  
Bacterial Infections ◽  
The United States ◽  
Lytic Infection ◽  
Health Concern ◽  
Early 20Th Century ◽  
Drug Resistant ◽  
Bacteriophage Therapy ◽  
Antibiotic Resistant ◽  
Macromolecular Drugs ◽  
Major Drug

Antibiotic-resistant infections present a serious health concern worldwide. It is estimated that there are 2.8 million antibiotic-resistant infections and 35,000 deaths in the United States every year. Such microorganisms include Acinetobacter, Enterobacterioceae, Pseudomonas, Staphylococcus and Mycobacterium. Alternative treatment methods are, thus, necessary to treat such infections. Bacteriophages are viruses of bacteria. In a lytic infection, the newly formed phage particles lyse the bacterium and continue to infect other bacteria. In the early 20th century, d’Herelle, Bruynoghe and Maisin used bacterium-specific phages to treat bacterial infections. Bacteriophages are being identified, purified and developed as pharmaceutically acceptable macromolecular “drugs,” undergoing strict quality control. Phages can be applied topically or delivered by inhalation, orally or parenterally. Some of the major drug-resistant infections that are potential targets of pharmaceutically prepared phages are Pseudomonas aeruginosa, Mycobacterium tuberculosis and Acinetobacter baumannii.

scholarly journals Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 150 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative

Bacterial infections involving antibiotic resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR) or extensive drug resistant (XDR) bacterial strains. Most recently, a novel acquired plasmid mediated resistance mechanism to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR and XDR gram-negative bacteria, has been reported. Plasmid mediated colistin resistant gram-negative bacteria have been described to be pan-drug resistant, implying a state devoid of alternative antibiotic therapeutic options. This review describes the evolution of antibiotic resistance to plasmid mediated colistin resistance, and discusses the potential role of high-throughput sequencing technologies, genomics and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antimicrobial resistance as a whole.

scholarly journals Bacteriophage therapy: experience from the Eliava Institute, Georgia

2008 ◽  
Vol 29 (2) ◽  
pp. 96 ◽  
Author(s):  
Nina Chanishvili ◽  
Richard Sharp
Keyword(s):  
Soviet Union ◽  
Former Soviet Union ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Effective Means ◽  
Resistant Bacteria ◽  
Bacteriophage Therapy ◽  
Antibiotic Resistant ◽  
Bacterial Diseases ◽  
Wide Range

The lysis of bacteria by bacteriophage was independently discovered by Frederick Twort and Felix d?Herelle but it was d?Herelle who proposed that bacteriophage might be applied to the control of bacterial diseases. Within the former Soviet Union (FSU), bacteriophage therapy was researched and applied extensively for the treatment of a wide range of bacterial infections. In the West, however, it was not explored with the same enthusiasm and was eventually discarded with the arrival of antibiotics. However, the increase in the incidence of multi-antibiotic-resistant bacteria and the absence of effective means for their control has led to increasing international interest in phage therapy and in the long experience of the Eliava Institute. The Eliava Institute of Bacteriophage, Microbiology and Virology (IBMV), which celebrates its 85th anniversary in 2008, was founded in Tbilisi in 1923 through the joint efforts of d?Herelle and the Georgian microbiologist, George Eliava.

scholarly journals Do phenothiazines possess antimicrobial and efflux inhibitory properties?

2019 ◽  
Author(s):  
Elizabeth M Grimsey ◽  
Laura J V Piddock
Keyword(s):  
Bacterial Infections ◽  
Bacterial Population ◽  
Selective Pressure ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Phenothiazine Derivatives ◽  
Antipsychotic Medications ◽  
Development Of Resistance ◽  
Medical Advances

ABSTRACTAntibiotic resistance is a global health concern; the rise of drug-resistant bacterial infections is compromising the medical advances that resulted from the introduction of antibiotics at the beginning of the 20th century. Considering that the presence of mutations within individuals in a bacterial population may allow a subsection to survive and propagate in response to selective pressure, as long as antibiotics are used in the treatment of bacterial infections, development of resistance is an inevitable evolutionary outcome. This, combined with the lack of novel antibiotics being released to the clinical market, means the need to develop alternative strategies to treat these resistant infections is critical. We discuss how the use of antibiotic adjuvants can minimise the appearance and impact of resistance. To this effect, several phenothiazine-derived drugs have been shown to potentiate the activities of antibiotics used to treat infections caused by Gram-positive and Gram-negative bacteria. Outside of their role as antipsychotic medications, we review the evidence to suggest that phenothiazines possess inherent antibacterial and efflux inhibitory properties enabling them to potentially combat drug resistance. We also discuss that understanding their mode of action is essential to facilitate the design of new phenothiazine derivatives or novel agents for use as antibiotic adjuvants.

Tea: An anti-bacterial agent against drug resistant bacteria

2021 ◽  
Vol 15 (10) ◽  
pp. 2506-2511
Author(s):  
Nayyab Sultan ◽  
Sabahat Javaid Butt ◽  
Wajeeha Mehak ◽  
Samreen Qureshi ◽  
Syed Hamza Abbas ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Salmonella Typhi ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Bacterial Agent ◽  
Drug Resistant Bacteria ◽  
Scientific World

Antibiotics have played a crucial role in the treatment of bacterial infections. Past few decades are marked with advancement of multidrug resistant (MDR) pathogens, which have endangered antibiotic’s therapeutic efficacy. Scientific world is now struggling with the crisis of MDR pathogens. This supreme matter demands careful attention or otherwise it would jeopardize clinical management of infectious diseases. Implication of alternative approaches can pave a new way in the treatment of these troublesome bacteria. Tea leaves are known to pose antibacterial activity against many pathogenic microorganisms. This review has summarized the antibacterial potential of tea leave’s extracts against resistant bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter pylori, Escherichia coli, Klebsiella pneumonia, Salmonella typhi, Acenitobacter spp, Campylobacter spp. Consumption of natural products such as tea may very well replace, minimize or obliterate this complicated situation. Keywords: Anti-bacterial, Tea, Camellia sinensis, Drug resistant bacteria, Antibiotic resistant bacteria, Synergism, Polyphenols.

scholarly journals Bacteriophage therapy for bone and joint infections

2021 ◽  
Vol 103-B (2) ◽  
pp. 234-244
Author(s):  
Bryan P. Gibb ◽  
Michael Hadjiargyrou
Keyword(s):  
Bacterial Infections ◽  
Current Knowledge ◽  
Joint Infection ◽  
Bacteriophage Therapy ◽  
Antibiotic Resistant ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
Orthopaedic Infections

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244.

scholarly journals Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against Drug-Resistant Acinetobacter baumannii

2018 ◽  
Vol 19 (10) ◽  
pp. 3041 ◽  
Author(s):  
Min Kim ◽  
Na Kang ◽  
Su Ko ◽  
Jonggwan Park ◽  
Eunji Park ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
High Stability ◽  
Therapeutic Agents ◽  
Antibiofilm Activity ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Biofilm Inhibition ◽  
Antibiotic Resistant

Antimicrobial peptides (AMPs) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. Previous studies showed that magainin 2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. The present study was conducted to investigate the antibacterial activity of magainin 2 against Acinetobacter baumannii. Magainin 2 showed excellent antibacterial activity against A. baumannii strains and high stability at physiological salt concentrations. This peptide was not cytotoxic towards HaCaT cells and showed no hemolytic activity. Biofilm inhibition and elimination were significantly induced in all A. baumannii strains exposed to magainin 2. We confirmed the mechanism of magainin 2 on the bacterial outer and inner membranes. Collectively, these results suggest that magainin 2 is an effective antimicrobial and antibiofilm agent against A. baumannii strains.

scholarly journals Economic Evaluation of FebriDx®: A Novel Rapid, Point-of-Care Test for Differentiation of Viral versus Bacterial Acute Respiratory Infection in the United States

2021 ◽  
Vol 8 (2) ◽  
pp. 56-62
Author(s):  
Katherine Dick ◽  
John Schneider
Keyword(s):  
United States ◽  
Economic Evaluation ◽  
Antibiotic Treatment ◽  
Bacterial Infections ◽  
Point Of Care ◽  
The United States ◽  
Antibiotic Prescribing ◽  
Point Of Care Testing ◽  
Antibiotic Resistant ◽  
Point Of Care Test

Background: Acute respiratory infections (ARIs) are commonly treated with antibiotics in outpatient settings, but many infections are caused by viruses and antibiotic treatment is therefore inappropriate. FebriDx®, a rapid point-of-care test that can differentiate viral from bacterial infections, can inform antibiotic treatment decisions. Objectives: The primary aim of this study is to conduct a literature-based US economic evaluation of a novel rapid point-of-care test, FebriDx®, that simultaneously measures two key infection biomarkers, C-reactive protein (CRP) and\ Myxovirus resistance protein A (MxA), to accurately differentiate viral from bacterial infection. Methods: A budget impact model was developed based on a review of published literature on antibiotic prescribing for ARIs in the United States. The model considers the cost of antibiotic treatment, antibiotic resistant infections, antibiotic-related adverse events, and point-of-care testing. These costs were extrapolated to estimate savings on a national level. Results: The expected national cost to treat ARIs under standard of care was US $8.25 billion, whereas the expected national cost of FebriDx point-of-care-guided ARI treatment was US $5.74 billion. Therefore, the expected national savings associated with FebriDx® rapid point-of-care testing was US $2.51 billion annually. Conclusions: FebriDx, a point of care test that can reliably aid in the differentiation of viral and bacterial infections, can reduce antibiotic misuse and, therefore, antibiotic resistant infections. This results in significant cost savings, driven primarily by the reduction in antibiotic resistant infections.

scholarly journals Fosfomycin

2016 ◽  
Vol 29 (2) ◽  
pp. 321-347 ◽  
Author(s):  
Matthew E. Falagas ◽  
Evridiki K. Vouloumanou ◽  
George Samonis ◽  
Konstantinos Z. Vardakas
Keyword(s):  
Bacterial Infections ◽  
Clinical Effectiveness ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Development Of Resistance ◽  
Extensively Drug Resistant ◽  
New Antibiotics

SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

scholarly journals Lessons Learned From the First 10 Consecutive Cases of Intravenous Bacteriophage Therapy to Treat Multidrug-Resistant Bacterial Infections at a Single Center in the United States

2020 ◽  
Vol 7 (9) ◽  
Author(s):  
Saima Aslam ◽  
Elizabeth Lampley ◽  
Darcy Wooten ◽  
Maile Karris ◽  
Constance Benson ◽  
...  
Keyword(s):  
United States ◽  
Bacterial Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Lessons Learned ◽  
Successful Outcome ◽  
Bacteriophage Therapy ◽  
Successful Case

Abstract Background Due to increasing multidrug-resistant (MDR) infections, there is an interest in assessing the use of bacteriophage therapy (BT) as an antibiotic alternative. After the first successful case of intravenous BT to treat a systemic MDR infection at our institution in 2017, the Center for Innovative Phage Applications and Therapeutics (IPATH) was created at the University of California, San Diego, in June 2018. Methods We reviewed IPATH consult requests from June 1, 2018, to April 30, 2020, and reviewed the regulatory process of initiating BT on a compassionate basis in the United States. We also reviewed outcomes of the first 10 cases at our center treated with intravenous BT (from April 1, 2017, onwards). Results Among 785 BT requests to IPATH, BT was administered to 17 of 119 patients in whom it was recommended. One-third of requests were for Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus. Intravenous BT was safe with a successful outcome in 7/10 antibiotic-recalcitrant infections at our center (6 were before IPATH). BT may be safely self-administered by outpatients, used for infection suppression/prophylaxis, and combined successfully with antibiotics despite antibiotic resistance, and phage resistance may be overcome with new phage(s). Failure occurred in 2 cases despite in vitro phage susceptibility. Conclusions We demonstrate the safety and feasibility of intravenous BT for a variety of infections and discuss practical considerations that will be critical for informing future clinical trials.

scholarly journals A Synthetic Antibiotic Scaffold Effective Against Multidrug-Resistant Bacterial Pathogens

2021 ◽  
Author(s):  
Matthew Mitcheltree ◽  
Amarnath Pisipati ◽  
Egor A. Syroegin ◽  
Katherine J. Silvestre ◽  
Dorota Klepacki ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Ribosomal Subunit ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Structural Basis ◽  
Resistant Bacteria ◽  
Global Public Health ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Orally Bioavailable

The dearth of new medicines effective against antibiotic-resistant bacteria presents a growing global public health concern. For more than five decades, the search for new antibiotics has relied heavily upon the chemical modification of natural products (semi-synthesis), a method ill-equipped to combat rapidly evolving resistance threats. Semi-synthetic modifications are typically of limited scope within polyfunctional antibiotics, usually increase molecular weight, and seldom permit modifications of the underlying scaffold. When properly designed, fully synthetic routes can easily address these shortcomings. Here we report the structure-guided design and component-based synthesis of a rigid oxepanoproline scaffold which, when linked to the aminooctose residue of clindamycin, produces an antibiotic of exceptional potency and spectrum of activity, here named iboxamycin. Iboxamycin is effective in strains expressing Erm and Cfr rRNA methyltransferase enzymes, products of genes that confer resistance to all clinically relevant antibiotics targeting the large ribosomal subunit, namely macrolides, lincosamides, phenicols, oxazolidinones, pleuromutilins, and streptogramins. X-ray crystallographic studies of iboxamycin in complex with the native 70S bacterial ribosome, as well as the Erm-methylated 70S ribosome, uncover the structural basis for this enhanced activity, including an unforeseen and unprecedented displacement of upon antibiotic binding. In mice, iboxamycin is orally bioavailable, safe, and effective in treating bacterial infections, testifying to the capacity for chemical synthesis to provide new antibiotics in an era of rising resistance.

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