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Stephen T Abedon - One of the best experts on this subject based on the ideXlab platform.
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Phage Therapy: Emergent Property Pharmacology
Journal of Bioanalysis & Biomedicine, 2020Co-Authors: Andrew J. Curtright, Stephen T AbedonAbstract:Phage Therapy is the application to bodies of bacterioPhages – the viruses of bacteria. This is done to combat bacterial infections. In this article we combine three themes, Phage Therapy, pharmacology, and the concept of emergent properties. We do this to explore what is unique along with what is not so unique about Phage Therapy, as viewed from a pharmacological standpoint. At the same time, we consider the place of Phage Therapy, and drugs generally, within the larger scheme that is biology. We make these latter considerations predominantly in terms of emergent properties, which are system characteristics that exist, qualitatively, at ‘higher’ but not ‘lower’ levels of organization. The latter is a relevant consideration especially in exploring the pharmacology of ‘living’ antibacterials, as are Phages, which at lower levels can be viewed as collections of numerous molecules and biochemical pathways but which at higher levels become organized into somewhat complex entities that are capable of ‘self amplification’. Emergent properties are also prominently relevant to pharmacology, more generally, as they give rise to requirements for animal along with clinical testing to identify otherwise unexpected drug characteristics. Our broader goal is to stimulate a better integration of issues of Phage Therapy and pharmacology, predominantly in light of the substantial complexity of Phages in comparison with chemical drugs and towards furthering the rational development of Phagebased antibacterial strategies. Our chief conclusion is that while Phages, due to their complexity, potentially possess numerous emergent properties when compared with less-complex antibacterials, in fact other aspects of Phages – including their relative benignness, environmental ubiquity, and that their antibacterial properties are products of evolution – can allow for certain simplifications to pharmacological development. These simplifications are not as readily achieved by chemical drugs, such as antibiotics, which can possess negative properties that are difficult to predict.
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Phage Therapy: The Pharmacology of Antibacterial Viruses.
Current issues in molecular biology, 2020Co-Authors: Katarzyna Danis-wlodarczyk, Krystyna Dąbrowska, Stephen T AbedonAbstract:Pharmacology can be differentiated into two key aspects, pharmacodynamics and pharmacokinetics. Pharmacodynamics describes a drug's impact on the body while pharmacokinetics describes the body's impact on a drug. Another way of understanding these terms is that pharmacodynamics is a description of both the positive and negative consequences of drugs attaining certain concentrations in the body while pharmacokinetics is concerned with our ability to reach and then sustain those concentrations. Unlike the drugs for which these concepts were developed, including antibiotics, the bacterioPhages (or 'Phages') that we consider here are not chemotherapeutics but instead are the viruses of bacteria. Here we review the pharmacology of these viruses, particularly as they can be employed to combat bacterial infections (Phage Therapy). Overall, an improved pharmacological understanding of Phage Therapy should allow for more informed development of Phages as antibacterial 'drugs', allow for more rational post hoc debugging of Phage Therapy experiments, and encourage improved design of Phage Therapy protocols. Contrasting with antibiotics, however, Phages as viruses impact individual bacterial cells as single virions rather than as swarms of molecules, and while they are killing bacteria, bacterioPhages also can amplify Phage numbers, in situ. Explorations of Phage Therapy pharmacology consequently can often be informed as well by basic principles of the ecological interactions between Phages and bacteria as by study of the pharmacology of drugs. BacterioPhages in Phage Therapy thus can display somewhat unique as well as more traditional pharmacological aspects.
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Pharmacologically Aware Phage Therapy: Pharmacodynamic and Pharmacokinetic Obstacles to Phage Antibacterial Action in Animal and Human Bodies.
Microbiology and Molecular Biology Reviews, 2019Co-Authors: Krystyna Dąbrowska, Stephen T AbedonAbstract:SUMMARY The use of viruses infecting bacteria (bacterioPhages or Phages) to treat bacterial infections has been ongoing clinically for approximately 100 years. Despite that long history, the growing international crisis of resistance to standard antibiotics, abundant anecdotal evidence of efficacy, and one successful modern clinical trial of efficacy, this Phage Therapy is not yet a mainstream approach in medicine. One explanation for why Phage Therapy has not been subject to more widespread implementation is that Phage Therapy research, both preclinical and clinical, can be insufficiently pharmacologically aware. Consequently, here we consider the pharmacological obstacles to Phage Therapy effectiveness, with Phages in Phage Therapy explicitly being considered to serve as drug equivalents. The study of pharmacology has traditionally been differentiated into pharmacokinetic and pharmacodynamic aspects. We therefore separately consider the difficulties that Phages as virions can have in traveling through body compartments toward reaching their target bacteria (pharmacokinetics) and the difficulties that Phages can have in exerting antibacterial activity once they have reached those bacteria (pharmacodynamics). The latter difficulties, at least in part, are functions of Phage host range and bacterial resistance to Phages. Given the apparently low toxicity of Phages and the minimal side effects of Phage Therapy as practiced, Phage Therapy should be successful so long as Phages can reach the targeted bacteria in sufficiently high numbers, adsorb, and then kill those bacteria. Greater awareness of what obstacles to this success generally or specifically can exist, as documented in this review, should aid in the further development of Phage Therapy toward wider use.
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information Phage Therapy research should report
Pharmaceuticals, 2017Co-Authors: Stephen T AbedonAbstract:BacterioPhages, or Phages, are viruses which infect bacteria. A large subset of Phages infect bactericidally and, consequently, for nearly one hundred years have been employed as antibacterial agents both within and outside of medicine. Clinically these applications are described as Phage or bacterioPhage Therapy. Alternatively, and especially in the treatment of environments, this practice instead may be described as a Phage-mediated biocontrol of bacteria. Though the history of Phage Therapy has involved substantial clinical experimentation, current standards along with drug regulations have placed a premium on preclinical approaches, i.e., animal experiments. As such, it is important for preclinical experiments not only to be held to high standards but also to be reported in a manner which improves translation to clinical utility. Here I address this latter issue, that of optimization of reporting of preclinical as well as clinical experiments. I do this by providing a list of pertinent information and data which, in my opinion, Phage Therapy experiments ought to present in publications, along with tips for best practices. The goal is to improve the ability of readers to gain relevant information from reports on Phage Therapy research, to allow other researchers greater potential to repeat or extend findings, to ease transitions from preclinical to clinical development, and otherwise simply to improve Phage Therapy experiments. Targeted are not just authors but also reviewers, other critical readers, writers of commentaries, and, perhaps, formulators of guidelines or policy. Though emphasizing Therapy, many points are applicable to Phage-mediated biocontrol of bacteria more generally.
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Phage Therapy: eco-physiological pharmacology.
Scientifica, 2014Co-Authors: Stephen T AbedonAbstract:Bacterial virus use as antibacterial agents, in the guise of what is commonly known as Phage Therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of Phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to Phage infections of pathogens, and also patient responses to Phage virions alone. Ecologically, we can consider Phage propagation, densities, distribution (within bodies), impact on body-associated microbiota (as ecological communities), and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view Phages during Phage Therapy in pharmacological terms. The relatively unique status of Phages within the context of Phage Therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of Phage Therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.
Andrzej Górski - One of the best experts on this subject based on the ideXlab platform.
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Ethics of Phage Therapy
Phage Therapy: A Practical Approach, 2019Co-Authors: Jan Borysowski, Andrzej GórskiAbstract:Phage Therapy is an experimental method of treatment of antibiotic-resistant bacterial infections. Patients can get access to Phages either by enrolling in a clinical trial or during compassionate treatment. Very few clinical trials of Phages have been conducted to date. Therefore, so far most patients have got access to Phage Therapy on a compassionate use basis. The main objective of this chapter is to discuss main issues relevant to ethics of clinical trials and compassionate use of Phage Therapy. Discussion of compassionate use focuses on whether Phage Therapy is compliant with the four main principles of medical ethics including non-maleficence, beneficence, justice, and respect for the patient’s autonomy. Moreover, we discuss ethical guidelines which might be helpful for doctors who consider performing Phage Therapy on a compassionate use basis.
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Phage Therapy in Prostatitis: Recent Prospects.
Frontiers in Microbiology, 2018Co-Authors: Andrzej Górski, Marzanna Łusiak-szelachowska, Ewa Jończyk-matysiak, Jan Borysowski, Ryszard Międzybrodzki, Beata Weber-dąbrowska, Sławomir Letkiewicz, Natalia Bagińska, Karen S. SfanosAbstract:Prostatitis has various etiology including bacterial infection and dysregulated immunity; some of its forms remain a serious therapeutic challenge. Inflammation occurs in all forms of this disorder and is proposed to predispose to the development of prostate cancer. There are reports that Phage Therapy is effective in chronic bacterial prostatitis. Recent findings suggest that Phages not only eliminate bacteria, but also mediate immunomodulating (for example anti-inflammatory) functions. The immunomodulating effects of Phages could be beneficial in treating all forms of prostatitis and play some role in the prevention of the development of prostate cancer. As the etiological factors contributing to the majority of prostatitis cases remains largely unknown, and management options are often likewise limited, Phage Therapy merits further research as an attractive therapeutic option given its immunomodulating effects irrespective of the underlying causative factor(s).
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Phage Therapy what have we learned
Viruses, 2018Co-Authors: Andrzej Górski, Ryszard Miedzybrodzki, Jan Borysowski, Malgorzata łobocka, Aleksandra Glowackarutkowska, Agnieszka Bednarek, Ewa Jonczykmatysiak, Marzanna łusiakszelachowska, Beata Weberdąbrowska, Natalia BaginskaAbstract:In this article we explain how current events in the field of Phage Therapy may positively influence its future development. We discuss the shift in position of the authorities, academia, media, non-governmental organizations, regulatory agencies, patients, and doctors which could enable further advances in the research and application of the Therapy. In addition, we discuss methods to obtain optimal Phage preparations and suggest the potential of novel applications of Phage Therapy extending beyond its anti-bacterial action.
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Can Phage Therapy solve the problem of recalcitrant chronic rhinosinusitis
Future Microbiology, 2017Co-Authors: Joanna Szaleniec, Andrzej Górski, Maciej Szaleniec, Ryszard Międzybrodzki, Beata Weber-dąbrowska, Paweł Stręk, Jacek SkładzieńAbstract:: Chronic rhinosinusitis (CRS) affects 5-15% of the global population. In some patients, the infectious exacerbations of the disease are recalcitrant to medical treatment and surgery. These cases are probably associated with the presence of bacterial biofilms. BacterioPhage (Phage) Therapy seems to be a promising antibiofilm strategy. The efficacy of Phage Therapy in sinonasal infections has been demonstrated both in vitro and in animal models. In the past, Phage preparations were also administered to humans with CRS with favorable outcomes and no significant side effects. Very recently, the safety and efficacy of Phage Therapy in otolaryngological infections has been demonstrated in pioneer Phase I/II clinical trials. This review addresses the potential of Phage Therapy to treat CRS. We also discuss issues that require further research.
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Delivering Phage Therapy per os: benefits and barriers
Expert Review of Anti-Infective Therapy, 2017Co-Authors: Susan Zelasko, Andrzej Górski, Krystyna DabrowskaAbstract:INTRODUCTION: Multidrug-resistant bacterial infections of the gastrointestinal tract pose a serious public health concern. High levels of antibiotic drug resistance, along with the potential for antibiotics to precipitate disease or alter the gut microbiome has prompted research into alternative treatment methods. Evidence suggests that bacterioPhage Therapy delivered per os may be well-suited to target such infections. Areas covered: Herein, we discuss the specific advantages and challenges of using orally administered Phage Therapy. Our literature review encompasses recent works using Phages to target various clinically-relevant bacteria in vivo. We also provide insights into methods that aim to overcome the barriers to effective Phage transit through the harsh gastrointestinal environment. Expert commentary: Evidence from a number of in vivo animal studies suggests that targeting bacterial infections using Phages delivered orally holds potential. Efficacious oral Phage Therapy depends on the delivery of sufficient Phage titers to the infection site, which may be hindered by the host's gastrointestinal tract and immune response.
Ryszard Miedzybrodzki - One of the best experts on this subject based on the ideXlab platform.
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Phage Therapy in orthopaedic implant associated infections
2019Co-Authors: Paweł Rogóz, Ryszard Miedzybrodzki, Wojciech Fortuna, Beata Weberdąbrowska, Derek F Amanatullah, Robert Manasherob, N V Tikunova, Slawomir LetkiewiczAbstract:Implant-associated infection (IAI) remains a significant issue in orthopaedic surgery. BacterioPhages are naturally occurring viruses that kill bacteria. BacterioPhages are being considered as a reliable alternative and/or adjunct to antibiotics, especially with the rise of multidrug-resistant bacterial strains. The isolation of bacterioPhages from the environment against major bacterial pathogens may be easier than searching for new antibiotics against these virulent bacterial stains. Although bacterioPhages are not pathogenic to mammalian cells, they induce a humoral immune response in a mammalian host resulting in the formation of anti-Phage antibodies that can influence the effect of Phage Therapy. We detail the experiences of several centers in Poland, the Republic of Georgia, the Russian Federation, and France that have extensive experience with Phage Therapy for IAI. Phage Therapy is an emerging new paradigm for the treatment of IAI as multidrug-resistant bacteria become more common and national governments as well as global health agencies push to improve antibiotic stewardship in clinical practice.
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Phage Therapy what have we learned
Viruses, 2018Co-Authors: Andrzej Górski, Ryszard Miedzybrodzki, Jan Borysowski, Malgorzata łobocka, Aleksandra Glowackarutkowska, Agnieszka Bednarek, Ewa Jonczykmatysiak, Marzanna łusiakszelachowska, Beata Weberdąbrowska, Natalia BaginskaAbstract:In this article we explain how current events in the field of Phage Therapy may positively influence its future development. We discuss the shift in position of the authorities, academia, media, non-governmental organizations, regulatory agencies, patients, and doctors which could enable further advances in the research and application of the Therapy. In addition, we discuss methods to obtain optimal Phage preparations and suggest the potential of novel applications of Phage Therapy extending beyond its anti-bacterial action.
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antibody production in response to staphylococcal ms 1 Phage cocktail in patients undergoing Phage Therapy
Frontiers in Microbiology, 2016Co-Authors: Maciej żaczek, Barbara Owczarek, Ryszard Miedzybrodzki, Wojciech Fortuna, Agnieszka Kopciuch, Ewa Jonczykmatysiak, Marzanna łusiakszelachowska, Beata Weberdąbrowska, Paweł RogózAbstract:In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiPhage antibodies) to a staphylococcal Phage cocktail in patients undergoing experimental Phage Therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wroclaw, Poland. We also evaluated whether occurring antiPhage antibodies had neutralizing properties towards applied Phages (K rate). Among 20 examined patients receiving the MS-1 Phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiPhage antibodies in their sera during Phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiPhage antibodies did not translate into unsatisfactory clinical results of Phage Therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiPhage antibodies before and during treatment. This may imply that possible induction of antiPhage antibodies is not an obstacle to the implementation of Phage Therapy and support our assumption that the outcome of the Phage treatment does not primarily depend on the appearance of antiPhage antibodies in sera of patients during Therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of Phage Therapy in humans.
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Antibody production in response to staphylococcal MS-1 Phage cocktail in patients undergoing Phage Therapy
Frontiers in Microbiology, 2016Co-Authors: Maciej żaczek, Barbara Owczarek, Marzanna Łusiak-szelachowska, Ewa Jończyk-matysiak, Beata Weber-dabrowska, Ryszard Miedzybrodzki, Wojciech Fortuna, Paweł Rogóz, Agnieszka Kopciuch, Andrzej GórskiAbstract:© 2016 Zaczek, Łusiak-Szelachowska, Jończyk-Matysiak, Weber-Dabrowska, Miedzybrodzki, Owczarek, Kopciuch, Fortuna, Rogóz and Górski. In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiPhage antibodies) to a staphylococcal Phage cocktail in patients undergoing experimental Phage Therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wroclaw, Poland. We also evaluated whether occurring antiPhage antibodies had neutralizing properties toward applied Phages (K rate). Among 20 examined patients receiving the MS-1 Phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiPhage antibodies in their sera during Phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiPhage antibodies did not translate into unsatisfactory clinical results of Phage Therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiPhage antibodies before and during treatment. This may imply that possible induction of antiPhage antibodies is not an obstacle to the implementation of Phage Therapy and support our assumption that the outcome of the Phage treatment does not primarily depend on the appearance of antiPhage antibodies in sera of patients during Therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of Phage Therapy in humans.
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clinical aspects of Phage Therapy
Advances in Virus Research, 2012Co-Authors: Ryszard Miedzybrodzki, Wojciech Fortuna, Paweł Rogóz, Jan Borysowski, Beata Weberdąbrowska, Slawomir Letkiewicz, Krzysztof Szufnarowski, Zdzislaw Pawelczyk, Marlena KlakAbstract:Abstract Phage Therapy (PT) is a unique method of treatment of bacterial infections using bacterioPhages (Phages)—viruses that specifically kill bacteria, including their antibiotic-resistant strains. Over the last decade a marked increase in interest in the therapeutic use of Phages has been observed, which has resulted from a substantial rise in the prevalence of antibiotic resistance of bacteria, coupled with an inadequate number of new antibiotics. The first, and so far the only, center of PT in the European Union is the Phage Therapy Unit (PTU) established at the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland in 2005. This center continues the rich tradition of PT in Poland, which dates from the early 1920s. The main objective of this chapter is to present a detailed retrospective analysis of the results of PT of 153 patients with a wide range of infections resistant to antibiotic Therapy admitted for treatment at the PTU between January 2008 and December 2010. Analysis includes the evaluation of both the efficacy and the safety of PT. In general, data suggest that PT can provide good clinical results in a significant cohort of patients with otherwise untreatable chronic bacterial infections and is essentially well tolerated. In addition, the whole complex procedure employed to obtain and characterize therapeutic Phage preparations, as well as ethical aspects of PT, is discussed.
Paweł Rogóz - One of the best experts on this subject based on the ideXlab platform.
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Phage Therapy in orthopaedic implant associated infections
2019Co-Authors: Paweł Rogóz, Ryszard Miedzybrodzki, Wojciech Fortuna, Beata Weberdąbrowska, Derek F Amanatullah, Robert Manasherob, N V Tikunova, Slawomir LetkiewiczAbstract:Implant-associated infection (IAI) remains a significant issue in orthopaedic surgery. BacterioPhages are naturally occurring viruses that kill bacteria. BacterioPhages are being considered as a reliable alternative and/or adjunct to antibiotics, especially with the rise of multidrug-resistant bacterial strains. The isolation of bacterioPhages from the environment against major bacterial pathogens may be easier than searching for new antibiotics against these virulent bacterial stains. Although bacterioPhages are not pathogenic to mammalian cells, they induce a humoral immune response in a mammalian host resulting in the formation of anti-Phage antibodies that can influence the effect of Phage Therapy. We detail the experiences of several centers in Poland, the Republic of Georgia, the Russian Federation, and France that have extensive experience with Phage Therapy for IAI. Phage Therapy is an emerging new paradigm for the treatment of IAI as multidrug-resistant bacteria become more common and national governments as well as global health agencies push to improve antibiotic stewardship in clinical practice.
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antibody production in response to staphylococcal ms 1 Phage cocktail in patients undergoing Phage Therapy
Frontiers in Microbiology, 2016Co-Authors: Maciej żaczek, Barbara Owczarek, Ryszard Miedzybrodzki, Wojciech Fortuna, Agnieszka Kopciuch, Ewa Jonczykmatysiak, Marzanna łusiakszelachowska, Beata Weberdąbrowska, Paweł RogózAbstract:In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiPhage antibodies) to a staphylococcal Phage cocktail in patients undergoing experimental Phage Therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wroclaw, Poland. We also evaluated whether occurring antiPhage antibodies had neutralizing properties towards applied Phages (K rate). Among 20 examined patients receiving the MS-1 Phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiPhage antibodies in their sera during Phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiPhage antibodies did not translate into unsatisfactory clinical results of Phage Therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiPhage antibodies before and during treatment. This may imply that possible induction of antiPhage antibodies is not an obstacle to the implementation of Phage Therapy and support our assumption that the outcome of the Phage treatment does not primarily depend on the appearance of antiPhage antibodies in sera of patients during Therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of Phage Therapy in humans.
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Antibody production in response to staphylococcal MS-1 Phage cocktail in patients undergoing Phage Therapy
Frontiers in Microbiology, 2016Co-Authors: Maciej żaczek, Barbara Owczarek, Marzanna Łusiak-szelachowska, Ewa Jończyk-matysiak, Beata Weber-dabrowska, Ryszard Miedzybrodzki, Wojciech Fortuna, Paweł Rogóz, Agnieszka Kopciuch, Andrzej GórskiAbstract:© 2016 Zaczek, Łusiak-Szelachowska, Jończyk-Matysiak, Weber-Dabrowska, Miedzybrodzki, Owczarek, Kopciuch, Fortuna, Rogóz and Górski. In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiPhage antibodies) to a staphylococcal Phage cocktail in patients undergoing experimental Phage Therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wroclaw, Poland. We also evaluated whether occurring antiPhage antibodies had neutralizing properties toward applied Phages (K rate). Among 20 examined patients receiving the MS-1 Phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiPhage antibodies in their sera during Phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiPhage antibodies did not translate into unsatisfactory clinical results of Phage Therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiPhage antibodies before and during treatment. This may imply that possible induction of antiPhage antibodies is not an obstacle to the implementation of Phage Therapy and support our assumption that the outcome of the Phage treatment does not primarily depend on the appearance of antiPhage antibodies in sera of patients during Therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of Phage Therapy in humans.
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clinical aspects of Phage Therapy
Advances in Virus Research, 2012Co-Authors: Ryszard Miedzybrodzki, Wojciech Fortuna, Paweł Rogóz, Jan Borysowski, Beata Weberdąbrowska, Slawomir Letkiewicz, Krzysztof Szufnarowski, Zdzislaw Pawelczyk, Marlena KlakAbstract:Abstract Phage Therapy (PT) is a unique method of treatment of bacterial infections using bacterioPhages (Phages)—viruses that specifically kill bacteria, including their antibiotic-resistant strains. Over the last decade a marked increase in interest in the therapeutic use of Phages has been observed, which has resulted from a substantial rise in the prevalence of antibiotic resistance of bacteria, coupled with an inadequate number of new antibiotics. The first, and so far the only, center of PT in the European Union is the Phage Therapy Unit (PTU) established at the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland in 2005. This center continues the rich tradition of PT in Poland, which dates from the early 1920s. The main objective of this chapter is to present a detailed retrospective analysis of the results of PT of 153 patients with a wide range of infections resistant to antibiotic Therapy admitted for treatment at the PTU between January 2008 and December 2010. Analysis includes the evaluation of both the efficacy and the safety of PT. In general, data suggest that PT can provide good clinical results in a significant cohort of patients with otherwise untreatable chronic bacterial infections and is essentially well tolerated. In addition, the whole complex procedure employed to obtain and characterize therapeutic Phage preparations, as well as ethical aspects of PT, is discussed.
Maciej żaczek - One of the best experts on this subject based on the ideXlab platform.
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antibody production in response to staphylococcal ms 1 Phage cocktail in patients undergoing Phage Therapy
Frontiers in Microbiology, 2016Co-Authors: Maciej żaczek, Barbara Owczarek, Ryszard Miedzybrodzki, Wojciech Fortuna, Agnieszka Kopciuch, Ewa Jonczykmatysiak, Marzanna łusiakszelachowska, Beata Weberdąbrowska, Paweł RogózAbstract:In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiPhage antibodies) to a staphylococcal Phage cocktail in patients undergoing experimental Phage Therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wroclaw, Poland. We also evaluated whether occurring antiPhage antibodies had neutralizing properties towards applied Phages (K rate). Among 20 examined patients receiving the MS-1 Phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiPhage antibodies in their sera during Phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiPhage antibodies did not translate into unsatisfactory clinical results of Phage Therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiPhage antibodies before and during treatment. This may imply that possible induction of antiPhage antibodies is not an obstacle to the implementation of Phage Therapy and support our assumption that the outcome of the Phage treatment does not primarily depend on the appearance of antiPhage antibodies in sera of patients during Therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of Phage Therapy in humans.
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Antibody production in response to staphylococcal MS-1 Phage cocktail in patients undergoing Phage Therapy
Frontiers in Microbiology, 2016Co-Authors: Maciej żaczek, Barbara Owczarek, Marzanna Łusiak-szelachowska, Ewa Jończyk-matysiak, Beata Weber-dabrowska, Ryszard Miedzybrodzki, Wojciech Fortuna, Paweł Rogóz, Agnieszka Kopciuch, Andrzej GórskiAbstract:© 2016 Zaczek, Łusiak-Szelachowska, Jończyk-Matysiak, Weber-Dabrowska, Miedzybrodzki, Owczarek, Kopciuch, Fortuna, Rogóz and Górski. In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiPhage antibodies) to a staphylococcal Phage cocktail in patients undergoing experimental Phage Therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wroclaw, Poland. We also evaluated whether occurring antiPhage antibodies had neutralizing properties toward applied Phages (K rate). Among 20 examined patients receiving the MS-1 Phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiPhage antibodies in their sera during Phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiPhage antibodies did not translate into unsatisfactory clinical results of Phage Therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiPhage antibodies before and during treatment. This may imply that possible induction of antiPhage antibodies is not an obstacle to the implementation of Phage Therapy and support our assumption that the outcome of the Phage treatment does not primarily depend on the appearance of antiPhage antibodies in sera of patients during Therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of Phage Therapy in humans.
