Alternative treatment modes for antibiotic-resistant bacterial pathogens have become a public health priority. Bacteriophages are bacterial viruses that infect and lyse bacterial cells. Since ...bacteriophages are frequently bacterial host species-specific and can often also infect antibiotic-resistant bacterial cells, they could represent ideal antimicrobials for fighting the antibiotic resistance crisis. The medical use of bacteriophages has become known as phage therapy. It is widely used in Russia, where phage cocktails are sold in pharmacies as an over-the-counter drug. However, no phage product has been registered for medical purposes outside of the former Soviet Union. The current Special Issue of Viruses contains a collection of papers from opinion leaders in the field who explore hurdles to the introduction of phage therapy in western countries. The articles cover diverse topics ranging from patent to regulatory issues, the targeting of suitable bacterial infections, and the selection and characterization of safe and efficient phage cocktails. Phage resistance is discussed, and gaps in our knowledge of phage–bacterium interactions in the mammalian body are revealed, while other articles explore the use of phages in food production and processing.
Bacteriophages (phages/viruses) need host bacteria to replicate and propagate. Primarily, a bacteriophage contains a head/capsid to encapsidate the genetic material. Some phages contain tails. Phages ...encode endolysins to hydrolyze bacterial cell wall. The two main classes of phages are lytic or virulent and lysogenic or temperate. In comparison with antibiotics, to deal with bacterial infections, phage therapy is thought to be more effective. In 1921, the use of phages against bacterial infections was first demonstrated. Later on, in humans, phage therapy was used to treat skin infections caused by Pseudomonas species. Furthermore, phages were successfully employed against infections in animals – calves, lambs, and pigs infected with Escherichia coli. In agriculture, for instance, phages have successfully been used e.g., Apple blossom infection, caused by Erwinia amylovora, was effectively catered with the use of bacteriophages. Bacteriophages were also used to control E. coli, Salmonella, Listeria, and Campylobacter contamination in food. Comparatively, phage display is a recently discovered technology, whereby, bacteriophages play a significant role. This review is an effort to collect almost recent and relevant information regarding applications and complications associated with the use of bacteriophages.
The rise of multidrug-resistant bacteria has resulted in an increased interest in phage therapy, which historically preceded antibiotic treatment against bacterial infections. To date, there have ...been no reports of serious adverse events caused by phages. They have been successfully used to cure human diseases in Eastern Europe for many decades. More recently, clinical trials and case reports for a variety of indications have shown promising results. However, major hurdles to the introduction of phage therapy in the Western world are the regulatory and legal frameworks. Present regulations may take a decade or longer to be fulfilled. It is of urgent need to speed up the availability of phage therapy.
Carbapenem-resistant
(CRAB) is a perilous nosocomial pathogen causing substantial morbidity and mortality. Current treatment options for CRAB are limited and suffer from pharmacokinetic limitations, ...such as high toxicity and low plasma levels. As a result, CRAB is declared as the top priority pathogen by the World Health Organization for the investment in new drugs. This urgent need for new therapies, in combination with faster FDA approval process, accelerated new drug development and placed several drug candidates in the pipeline. This article reviews available information about the new drugs and other therapeutic options focusing on agents in clinical or late-stage preclinical studies for the treatment of CRAB, and it evaluates their expected benefits and potential shortcomings.
Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including
We report on a method used ...to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR
infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an
isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the
infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
Background. Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against ...experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. Methods. In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined. Results. In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P < .001 vs untreated controls) and was comparable with ciprofloxacin monotherapy. Moreover, phage/ciprofloxacin combinations were highly synergistic, killing >6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation). Conclusions. Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration.
The gut microbiota has been implicated in the multifactorial pathophysiology of cardiometabolic diseases (CMD).Bacteriophage (phage) therapy offers precise modulation of the gut microbiota, targeting ...specific pathobionts while minimizing collateral damage to beneficial microbes.Studies highlight the therapeutic potential of phages in cardiometabolic diseases, including reductions in pathogenic bacteria and improvements in metabolic parameters.Challenges in developing phage therapy for CMD include identifying target bacteria, generating effective combinations of phages, product formulation, and strict production requirements.Temperate phages and phages with CRISPR-Cas machinery could alter (metabolic) the function of gut microbes to improve the CMD phenotype in the future.
The worldwide prevalence of cardiometabolic diseases (CMD) is increasing, and emerging evidence implicates the gut microbiota in this multifactorial disease development. Bacteriophages (phages) are viruses that selectively target a bacterial host; thus, phage therapy offers a precise means of modulating the gut microbiota, limiting collateral damage on the ecosystem. Several studies demonstrate the potential of phages in human disease, including alcoholic and steatotic liver disease. In this opinion article we discuss the potential of phage therapy as a predefined medicinal product for CMD and discuss its current challenges, including the generation of effective phage combinations, product formulation, and strict manufacturing requirements.
The worldwide prevalence of cardiometabolic diseases (CMD) is increasing, and emerging evidence implicates the gut microbiota in this multifactorial disease development. Bacteriophages (phages) are viruses that selectively target a bacterial host; thus, phage therapy offers a precise means of modulating the gut microbiota, limiting collateral damage on the ecosystem. Several studies demonstrate the potential of phages in human disease, including alcoholic and steatotic liver disease. In this opinion article we discuss the potential of phage therapy as a predefined medicinal product for CMD and discuss its current challenges, including the generation of effective phage combinations, product formulation, and strict manufacturing requirements.
This multidisciplinary expert panel opinion on bacteriophage therapy has been written in the context of a society that is confronted with an ever‐increasing number of antibiotic resistant bacteria. ...To avoid the return to a pre‐antibiotic era, alternative treatments are urgently needed. The authors aim to contribute to the opinion formation of relevant stakeholders on how to potentially develop an infrastructure and legislation that paves the way for the acceptance and re‐implementation of bacteriophage therapy.
Today's society is confronted with an ever‐increasing number of antibiotic resistant bacteria. To avoid the return to a pre‐antibiotic era, alternative treatments are urgently needed. Bacteriophage therapy is accepted and practiced in parts of Eastern Europe. However, agreement has yet to be made in the rest of the world on how to overcome hurdles and how to establish a functional and practical legal frame‐work that is flexible enough to exploit and further explore the specificity of bacteriophages as an antibacterial, while giving precedence to patient safety.
This paper aims to contribute to the opinion formation of relevant stakeholders on how to potentially develop an infrastructure and legislation that paves the way for the acceptance and re‐implementation of bacteriophage therapy. (Idea and design: Ville Friman)
Introduction: In light of the emergence of antibiotic-resistant bacteria, phage (bacteriophage) therapy has been recognized as a potential alternative or addition to antibiotics in Western medicine ...for use in humans.
Areas covered: This review assessed the scientific literature on phage therapy published between 1 January 2007 and 21 October 2019, with a focus on the successes and challenges of this prospective therapeutic.
Expert opinion: Efficacy has been shown in animal models and experimental findings suggest promise for the safety of human phagotherapy. Significant challenges remain to be addressed prior to the standardization of phage therapy in the West, including the development of phage-resistant bacteria; the pharmacokinetic complexities of phage; and any potential human immune response incited by phagotherapy.
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