scholarly journals Past and Future of Phage Therapy and Phage-Derived Proteins in Patients with Bone and Joint Infection

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2414
Author(s):  
Tristan Ferry ◽  
Camille Kolenda ◽  
Thomas Briot ◽  
Aubin Souche ◽  
Sébastien Lustig ◽  
...  

Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being “GMP-like”) targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally “phage therapy 2.0” has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial–academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.

10.3823/816 ◽  
2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Baraa M. AL-Taha ◽  
Jamal Wadi ◽  
Asem A. Shehabi

The term probiotic (prolife) is utilized to describe useful living microorganisms, intended to colonize the large bowel, when consumed in adequate amounts, they confer physiological health benefits to the host. In the last decade, probiotics have been widely used as a nutritional supplement and became a rapidly developing research topic that gained importance in medicine. Recent clinical trials have found that consumption of beneficial bacterial species can manipulate gut flora and reduce or prevent the development of certain serious diseases. This brief review article is intended to discuss the status of research on probiotics, and the value of their consumption in human health.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 318
Author(s):  
Gracja Topka-Bielecka ◽  
Bożena Nejman-Faleńczyk ◽  
Sylwia Bloch ◽  
Aleksandra Dydecka ◽  
Agnieszka Necel ◽  
...  

Phage therapy is one of main alternative option for antibiotic treatment of bacterial infections, particularly in the era of appearance of pathogenic strains revealing resistance to most or even all known antibiotics. Enterococcus faecalis is one of such pathogens causing serious human infections. In the light of high level of biodiversity of bacteriophages and specificity of phages to bacterial species or even strains, development of effective phage therapy depend, between others, on identification and characterization of a large collection of these viruses, including understanding of their interactions with host bacterial cells. Recently, isolation of molecular characterization of bacteriophage vB_EfaS-271, infecting E. faecalis strains have been reported. In this report, phage–host interactions are reported, including ability of vB_EfaS-271 to infect bacteria forming biofilms, efficiency of eliminating bacterial cells from cultures depending on multiplicity of infection (m.o.i.), toxicity of purified phage particles to mammalian cells, and efficiency of appearance of phage-resistant bacteria. The presented results indicate that vB_EfaS-271 can significantly decrease number of viable E. faecalis cells in biofilms and in liquid cultures and reveals no considerable toxicity to mammalian cells. Efficiency of formation of phage-resistant bacteria was dependent on m.o.i. and was higher when the virion-cell ratio was as high as 10 than at low (between 0.01 and 0.0001) m.o.i. values. We conclude that vB_EfaS-271 may be considered as a candidate for its further use in phage therapy.


2020 ◽  
Vol 42 (6) ◽  
pp. 6-11
Author(s):  
Michael J Love ◽  
Renwick C J Dobson ◽  
Craig Billington

The growing prevalence of antibiotic resistance is a global crisis. It is predicted that by 2050, antibiotic resistance-related deaths will exceed by 10 million per year. Thus, there is an urgent need for alternative strategies that can either replace or supplement antibiotic use. Bacteriophages and their encoded lytic proteins, called endolysins, have both shown promise as antibiotic alternatives. Bacteriophages were first investigated as therapeutics nearly a century ago, but the success of antibiotics led to phage therapy being largely abandoned in Western medicine until recently. While sporadic reports of life-saving successes in the ad hoc use of phage therapy have emerged, properly designed, robust clinical trials and clear regulatory guidelines are required before the true potential of phage therapy can be realized. In addition, despite endolysin research still being in its infancy, the early successes of endolysin-based therapeutics already entering clinical trials are an exciting glimpse into the future. No stone can be left unturned in the discovery and development of novel therapeutics if we are to ensure a future supply of effective treatments for bacterial infections.


Virologie ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Tristan Ferry ◽  
Camille Kolenda ◽  
Claude-Alexandre Gustave ◽  
Sébastien Lustig ◽  
Jérôme Josse ◽  
...  

Virologie ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 49-56
Author(s):  
Tristan Ferry ◽  
Camille Kolenda ◽  
Claude-Alexandre Gustave ◽  
Sébastien Lustig ◽  
Jérôme Josse ◽  
...  

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Stephanie LaVergne ◽  
Theron Hamilton ◽  
Biswajit Biswas ◽  
M Kumaraswamy ◽  
R T Schooley ◽  
...  

Abstract In the era of antibiotic resistance, alternative treatment options for multidrug-resistant bacterial infections are being explored. We present a case of multidrug-resistant Acinetobacter baumannii infection treated with bacteriophages. Clinical trials are needed to further investigate bacteriophage therapy as an option to treat multidrug-resistant bacterial infections.


Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 138 ◽  
Author(s):  
Danitza Romero-Calle ◽  
Raquel Guimarães Benevides ◽  
Aristóteles Góes-Neto ◽  
Craig Billington

Antimicrobial resistance is increasing despite new treatments being employed. With a decrease in the discovery rate of novel antibiotics, this threatens to take humankind back to a “pre-antibiotic era” of clinical care. Bacteriophages (phages) are one of the most promising alternatives to antibiotics for clinical use. Although more than a century of mostly ad-hoc phage therapy has involved substantial clinical experimentation, a lack of both regulatory guidance standards and effective execution of clinical trials has meant that therapy for infectious bacterial diseases has yet to be widely adopted. However, several recent case studies and clinical trials show promise in addressing these concerns. With the antibiotic resistance crisis and urgent search for alternative clinical treatments for bacterial infections, phage therapy may soon fulfill its long-held promise. This review reports on the applications of phage therapy for various infectious diseases, phage pharmacology, immunological responses to phages, legal concerns, and the potential benefits and disadvantages of this novel treatment.


1994 ◽  
Vol 13 (1) ◽  
pp. 79-85 ◽  
Author(s):  
N.J. Dent

Since the inception of the 1976 Food and Drug Administration (FDA) regulations governing preclinical toxicology, the world has seen an explosion of guidelines, principles, and regulations. The objective of this report is to clarify the situation in Europe as to the status of Good Laboratory Practices (GLPs). An overview of the harmonisation currently underway in Europe is given, although this changes frequently with new countries applying to join the European Community (EC) or undertaking aspects of GLP compliance. Where interactions have occurred between the GLPs and Good Clinical Practices (GCPs) (for example, clinical trials in analyses and bioequivalent studies), the status of clinical pathology and ancillary laboratories is discussed. Finally, particular auditing problems experienced within the EC are addressed. The general concept of GLP has changed very little since the inception of the 1976 FDA regulations governing preclinical toxicology; however, over the past 17 years, several other “good practices” have come into play and, most certainly, the original concept of toxicology and GLP has now been extended into many other scientific areas. Although this text deals primarily with GLP and GCP, the interaction between these two good practices and Good Manufacturing Practice cannot be divorced. The impact of toxicology as a precursor to clinical trials has been seen with the introduction of guidelines for the conduct of such studies. These, with other guidelines for the production of clinical trial materials, mean, in essence, that now the production of a new chemical entity from conception to marketing is completely covered by a series of guidelines and regulations-known colloquially as “the good practices.”


2019 ◽  
Vol 73 (1) ◽  
pp. 155-174 ◽  
Author(s):  
Shayla Hesse ◽  
Sankar Adhya

Burgeoning problems of antimicrobial resistance dictate that new solutions be developed to combat old foes. Use of lytic bacteriophages (phages) for the treatment of drug-resistant bacterial infections is one approach that has gained significant traction in recent years. Fueled by reports of experimental phage therapy cases with very positive patient outcomes, several early-stage clinical trials of therapeutic phage products have been launched in the United States. Eventual licensure enabling widespread access to phages is the goal; however, new paths to regulatory approval and mass-market distribution, distinct from those of small-molecule antibiotics, must be forged first. This review highlights unique aspects related to the clinical use of phages, including advantages to be reaped as well as challenges to be overcome.


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