Search

Cancer immunotherapies have been widely hailed as a breakthrough for cancer treatment in the last decade, epitomized by the unprecedented results observed with checkpoint blockade. Even so, only a minority of patients currently achieve durable remissions. In general, responsive patients appear to have either a high number of tumor neoantigens, a preexisting immune cell infiltrate in the tumor microenvironment, or an 'immune-active' transcriptional profile, determined in part by the presence of a type I interferon gene signature. These observations suggest that the therapeutic efficacy of immunotherapy can be enhanced through strategies that release tumor neoantigens and/or produce a pro-inflammatory tumor microenvironment. In principle, exogenous tumor-targeting bacteria offer a unique solution for improving responsiveness to immunotherapy. This review discusses how tumor-selective bacterial infection can modulate the immunological microenvironment of the tumor and the potential for combination with cancer immunotherapy strategies to further increase therapeutic efficacy. In addition, we provide a perspective on the clinical translation of replicating bacterial therapies, with a focus on the challenges that must be resolved to ensure a successful outcome.

Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed-healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed-healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage-cocktail) was encapsulated in a porous hydrogel dressing made with three-dimensional printing. The phage-cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full-thickness skin wound in diabetic mice. The phage-cocktail dressing released 1.7%-5.7% of the phages embedded in 24 h, and reduced between 37%-79% of the surface bacteria compared with the blank dressing (p <.05). The phage-cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full-thickness wound treated with a phage-cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage-cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage-cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re-epithelialization (p <.05). The slow-released phage has demonstrated positive effects in repairing diabetic skin wounds., (© 2024 Wiley Periodicals LLC.)

While phages hold promise as an antibiotic alternative, they encounter significant challenges in combating bacterial infections, primarily due to the emergence of phage-resistant bacteria. Bacterial defence mechanisms like superinfection exclusion, CRISPR, and restriction-modification systems can hinder phage effectiveness. Innovative strategies, such as combining different phages into cocktails, have been explored to address these challenges. This review delves into these defence mechanisms and their impact at each stage of the infection cycle, their challenges, and the strategies phages have developed to counteract them. Additionally, we examine the role of phage cocktails in the evolving landscape of antibacterial treatments and discuss recent studies that highlight the effectiveness of diverse phage cocktails in targeting essential bacterial receptors and combating resistant strains., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dental infections, such as apical Periodontitis, periodontitis, and peri-implantitis (PI), are closely associated with specific bacterial species, including Streptococcus mutans (S. mutans), Porphyromonas gingivalis (P. gingivalis), and Fusobacterium nucleatum (F. nucleatum), among others. Antibiotics are extensively utilized for prophylactic and therapeutic purposes in the treatment of dental infections and other dental-related issues. Unfortunately, the rapid emergence of antimicrobial resistance has accompanied the increased use of antibiotics in recent years. Specific bacterial pathogens have reached a critical stage of antibiotic resistance, characterized by the proliferation of pan-resistant strains and the scarcity of viable therapeutic alternatives. Therapeutic use of particular bacteriophage (phage) particles that target bacterial pathogens is one potential alternative to antibiotics that are now being seriously considered for treating bacterial illnesses. A kind of virus known as a phage is capable of infecting and eliminating bacteria. Because they can't infect cells in plants and animals, phages might be a harmless substitute for antibiotics. To control oral disorders including periodontitis and dental caries, several research have been conducted in this area to study and identify phages from human saliva and dental plaque. The capacity of these agents to disturb biofilms expands their effectiveness against dental plaque biofilms and oral pathogens in cases of periodontitis, PI, and apical periodontitis. This review summarizes the current antibacterial properties of phages used to treat a variety of dental infections, such as periodontitis, peri-implantitis, infected dentin, and apical periodontitis., (© 2024. The Author(s).)

The escalating prevalence of antibiotic-resistant bacterial infections necessitates urgent alternative therapeutic strategies. Phage therapy, which employs bacteriophages to specifically target pathogenic bacteria, emerges as a promising solution. This review examines the efficacy of phage therapy in zebrafish models, both embryos and adults, which are proven and reliable for simulating human infectious diseases. We synthesize findings from recent studies that utilized these models to assess phage treatments against various bacterial pathogens, including Enterococcus faecalis , Pseudomonas aeruginosa , Mycobacterium abscessus , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , and Escherichia coli . Methods of phage administration, such as circulation injection and bath immersion, are detailed alongside evaluations of survival rates and bacterial load reductions. Notably, combination therapies of phages with antibiotics show enhanced efficacy, as evidenced by improved survival rates and synergistic effects in reducing bacterial loads. We also discuss the transition from zebrafish embryos to adult models, emphasizing the increased complexity of immune responses. This review highlights the valuable contribution of the zebrafish model to advancing phage therapy research, particularly in the face of rising antibiotic resistance and the urgent need for alternative treatments., Competing Interests: The authors declare no conflict of interest.

Phage Therapy: WHERE DO WE STAND? Bacteriophages, discovered at the beginning of the 20th century by Félix d'Hérelle, are viruses that infect and destroy bacteria. Unlike antibiotics, phages are specific to a given bacterial species. After initial successes (shigellosis, cholera), the arrival of antibiotics overshadowed phage therapy. It was not until 2000, with the emergence of antibiotic resistance, that phages and phage therapy made a comeback. They have the status of medicines, but production remains limited. In France, treatments are carried out on a compassionate basis, with a number of isolated successes that need to be confirmed by clinical trials. Some trials are currently underway in France to assess the efficacy of phage therapy in combination with antibiotics. France, a pioneer in phage therapy in its early days and at the time of its comeback, seems to be slowing down in 2024 compared with its European neighbors. The adoption of phage therapy on a routine basis in France will still require time and significant progress., Competing Interests: A. Bleibtreu déclare avoir participé à des interventions ponctuelles pour Phaxiam. S. Diamantis est investigateur principal d’un essai thérapeutique financé par un PHRCN incluant des produits de la société Phaxiam.

Bacterial infections represent a significant global threat to human health, leading to considerable economic losses through increased healthcare costs and reduced productivity. One major challenge in treating these infections is the presence of biofilms - structured bacterial communities that form protective barriers, making traditional treatments less effective. Additionally, the rise of antibiotic-resistant bacteria has exacerbated treatment difficulties. To address these challenges, researchers are developing and exploring innovative approaches to combat biofilm-related infections. This mini-review highlights recent advancements in the following key areas: surface anti-adhesion technologies, electricity, photo/acoustic-active materials, endogenous mimicking agents, and innovative drug delivery systems. These strategies aim to prevent biofilm formation, disrupt existing biofilms, and enhance the efficacy of antimicrobial treatments. Currently, these approaches show great potential for applications in medical fields such as medical device and wound - associated biofilm infections. By summarizing these developments, this mini-review provides a comprehensive resource for researchers seeking to advance the management and treatment of biofilm-associated infections., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

The increasing global incidence of multidrug-resistant (MDR) bacterial infections threatens public health and compromises various aspects of modern medicine. Recognising the urgency of this issue, the World Health Organisation has prioritised the development of novel antimicrobials to combat ESKAPEE pathogens. Comprising Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli , such pathogens represent a spectrum of high to critical drug resistance, accounting for a significant proportion of hospital-acquired infections worldwide. In response to the waning efficacy of antibiotics against these resilient pathogens, phage therapy (PT) has emerged as a promising therapeutic strategy. This review provides a comprehensive summary of clinical research on PT and explores the translational journey of phages from laboratory settings to clinical applications. It examines recent advancements in pre-clinical and clinical developments, highlighting the potential of phages and their proteins, alone or in combination with antibiotics. Furthermore, this review underlines the importance of establishing safe and approved routes of phage administration to patients. In conclusion, the evolving landscape of phage therapy offers a beacon of hope in the fight against MDR bacterial infections, emphasising the imperative for continued research, innovation and regulatory diligence to realise its full potential in clinical practice.

Background: Sepsis is a leading cause of neonatal mortality, despite the availability of effective treatment of possible serious bacterial illness (PSBI), including when referral to a hospital is not feasible. Gaps in access and delivery worsened during COVID-19. We conducted embedded implementation research in Ethiopia and Kenya aimed at mitigating the impact of COVID-19 and addressing various implementation challenges to improve PSBI management., Methods: The implementation research projects were implemented at the subnational level in Ethiopia and Kenya between November 2020-June 2022 (Ethiopia) and December 2020-August 2022 (Kenya). Guided by the implementation research frameworks, both projects conducted mixed formative quantitative and exploratory research from April to May 2021, followed by summative evaluations conducted between June and July 2022. Frameworks encompassed Consolidated Framework for Implementation Research (CFIR), Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM), as well as health systems framework that incorporates cascades of care and World Health Organization Health Systems Building Blocks. Results were synthesized across the projects through document review and sharing cross-project measures and strategies through a project community of practice., Results: Despite differences in settings across the projects, cross-cutting facilitators included community health worker program and support, and existence of guidelines for PSBI management at primary care levels. Barriers included community attitudes towards seeking care for sick newborns, COVID-19 risks and fear, and lack of health care worker competence. Country-specific contextual barriers included supply chain issues, civil conflict (Ethiopia), and labor strikes (Kenya). Strategies chosen to mitigate barriers and support implementation and sustainability in both settings included leveraging community health workers to address resistance to care-seeking, health workers' training, COVID-19 infection prevention measures, stakeholder engagement, and advocacy to integrate PSBI management into existing programs, policies, and training. Other strategies addressing emerging project-specific barriers, included improving follow-up through a community health desk and PSBI mobile app (Kenya) and supply chain strengthening (Ethiopia). Both projects improved PSBI management coverage, increased adoption and uptake, and informed national policy changes supporting potential for sustainability., Conclusions: Pragmatic embedded implementation research effectively supports the identification of barriers and mapping to strategies designed to increase effective coverage of PSBI management when referral is not feasible during the COVID-19 pandemic. Despite differences in context, cross-cutting strategies identified could inform broader scale-up in the region, including during future health system shocks., (© 2024. The Author(s).)

Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines. At our center, PT is strictly controlled and monitored by a multidisciplinary taskforce. Each phage treatment follows the same pathway to ensure standardization and data quality. Within the PHAGEFORCE framework, we established a testing platform to gain insight in the safety and efficacy of PT, biodistribution, phage kinetics and the molecular interaction between phages and bacteria. The draining fluid is collected to determine the phage titer and bacterial load. In addition, all bacterial isolates are fully characterized by genome sequencing to monitor the emergence of phage resistance. We hereby present a standardized bench-to-bedside protocol to gain more insight in the kinetics and dynamics of PT for musculoskeletal infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bessems, Chen, Uyttebroek, Devolder, Lood, Verwimp, De Munter, Debaveye, Depypere, Spriet, Van Gerven, Dupont, Wagemans, van Noort, Lavigne, Metsemakers and Onsea.)

Recently, bacteriophages have been considered alternatives to antibacterial treatments. Infectious diseases continue to plague the world because bacteria can adapt and develop defence mechanisms against antibiotics. The growing incidence of antibiotic-resistant bacterial infections necessitated the development of new techniques for treating bacterial infections worldwide. Clinical trials have shown efficiency against antibiotic-resistant bacteria. However, scientists in future clinical trials should scrutinize phage resistance implications, assess combination strategies with antimicrobial agents and address challenges in phage therapy delivery for effective implementation.

The worldwide prevalence of antimicrobial resistance coupled with the unavailability of newer antibiotics, has brought the sharp focus back among the scientific community, towards the discovery of novel alternative therapeutics to tackle the menace. Consequently, in the current post-antibiotic era, 'Bacteriophage Therapy' has emerged as one of the most promising option to address this problem. Bacteriophages, actually discovered long back, has shown greater potential to kill various bacterial pathogens, including the resistant clinical ones. Some of the other advantages for the use of bacteriophage therapy to treat infectious diseases include, wider availability of these microorganisms in nature, host-specific action, absence of any significant side-effects in humans and most often also exhibiting a broader anti-bacterial potential. In the recent times, the potential of phage therapy has been demonstrated in various treatments, clinical trials and infection models across the globe, where even antibiotics have completely failed. To address the global threat of AMR, WHO and UN have jointly illustrated "One Health" approach, recently extending the context to bacteriophage therapy. Many pharmaceutical companies have also recently started employing bacteriophages for developing different kinds of formulations for catering to medical and other industries. It has even shown great effect as combinatorial therapy along with antibiotics, to treat or manage various critical antibiotic resistant clinical infections. This continuously expanding potential of the bacteriophages holds great promise in the future, in the fight against the rising threat of AMR globally., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Infectious diseases lead to significant morbidity and mortality. Often, resolution of the acute stage of the disease leads to microbial persistence, resulting in chronic debilitating disease. Management of persistent infections frequently requires lifelong therapy with antimicrobial agents. These infections could be chronic viral infections like HIV, hepatitis B or chronic bacterial persistent infections like prosthetic joint infections caused by multi-drug resistant organisms. Bacteriophages have been designed specifically to target recalcitrant bacterial infections, such as prosthetic joint infections with varying success. In this review, we describe the historic evolution of scenarios and risks associated with innovative therapy using infectious agents to treat other persistent infections.

Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of Salmonella Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection. We found that the immune checkpoint T-cell immunoglobulin and ITIM domain (TIGIT) was significantly upregulated on lymphocytes during infection, particularly on CD4 + T cells, drastically limiting their proinflammatory function. Blockade of TIGIT in vivo using monoclonal antibodies was able to enhance immunity and improve bacterial clearance. The efficacy of anti-TIGIT was dependent on the capacity of the antibody to bind to Fc (fragment crystallizable) receptors, giving important insights into the mechanism of anti-TIGIT therapy. This research suggests that targeting immune checkpoints, such as TIGIT, has the potential to enhance immune responses toward bacteria and restore antibacterial treatment options in the face of antibiotic resistance., (© 2024 The Author(s). Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

The bacteriolytic character of bacteriophages was employed as antibacterial therapy almost from the time of their discovery in 1917. In the United States, phage therapy was sporadic during the 1920s and 1930s but had dwindled into obscurity by the post-WWII period. This demise of phage therapy has traditionally been attributed to the superiority of antibiotics, discovered and first used during the war years, but this explanation is complicated by the fact that phage therapy outside the United States has had a longer and more successful life, especially in the countries of Eastern Europe. This review considers another, probably synergetic factor that was specific to the medical uses of phage in the United States: the geopolitical climate fostered by the Cold War reaction against Soviet science and its associated specter, socialized medicine. This analysis suggests that even such a purely scientific matter involving bacterial viruses cannot escape social forces and political ideologies.

Mandarin fish (Siniperca chuatsi) is a prominent freshwater species with significant economic value in China, while disease poses a major hindrance to the advancement of mandarin fish aquaculture. To date, the understanding of the prevention and management of bacterial disease in mandarin fish remains incomplete. Therefore, there is a need for more comprehensive insights into the preventive and curative strategies to address these bacterial infections. In this review, we summarize the information pertaining to the predominant bacterial pathogens such as Aeromonas spp., Flavobacterium columnare, Edwardsiella tarda, Streptococcus uberis and Vibrio cholerae in the mandarin fish aquaculture, and point out the current strategies for diagnosis and combating these bacterial pathogens, as well as deliberate on the prospective alternative treatments such as vaccines, herbal remedies, and phage therapy for the prevention and control of these bacterial diseases. Furthermore, we also highlights the importance to implement an integrated bacterial disease management (IBDM) approach for the prevention and control of these pathogenic bacteria in aquaculture., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The rise of antibiotic-resistant strains demands new alternatives in antibacterial treatment. Bacteriophages, with their precise host specificity and ability to target and eliminate bacteria safely, present a valuable option. Meanwhile, hydrogels, known for their excellent biodegradability and biocompatibility, serve as ideal carriers for bacteriophages. The combination of bacteriophages and hydrogels ensures heightened phage activity, concentration, controlled release, and strong antibacterial properties, making it a promising avenue for antibacterial treatment. This article provides a comprehensive review of different crosslinking methods for phage hydrogels, focusing on their application in treating infections caused by various drug-resistant bacteria and highlighting their effective antibacterial properties and controlled release capabilities.

The emergence and increase in antimicrobial resistance (AMR) is now widely recognized as a major public health challenge. Traditional antimicrobial drugs are becoming increasingly ineffective, while the development of new antibiotics is waning. As a result, alternative treatments for infections are garnering increased interest. Among these alternatives, bacteriophages, also known as phages, are gaining renewed attention and are reported to offer a promising solution to alleviate the burden of bacterial infections. This review discusses the current successes of phage therapy (PT) against multidrug-resistant organisms (MDROs), such as Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Enterobacter spp. The review also compares the efficacy of PT with that of chemical antibiotics, reporting on its benefits and limitations, while highlighting its impact on the human gut microbiome and immune system. Despite its potential, phage therapy is reported to face challenges such as the narrow antibacterial range, the complexity of developing phage cocktails, and the need for precise dosing and duration protocols. Nevertheless, continued research, improved regulatory frameworks, and increased public awareness are essential to realize its full potential and integration into standard medical practice, paving the way for innovative treatments that can effectively manage infections in an era of rising antimicrobial resistance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Bacterial infection is one of the most problematic issues for human health and the resistance of bacteria to traditional antibiotics is a matter of huge concern. Therefore, research is focusing on the development of new strategies to efficiently kill these microorganisms. Recently, melanin is starting to be investigated for this purpose. Indeed, this very versatile material presents outstanding photothermal properties, already studied for photothermal therapy, which can be very useful for the light-induced eradication of bacteria. In this review, we present antibacterial melanin applications based on the photothermal effect, focusing both on the single action of melanin and on its combination with other antibacterial systems. Melanin, also thanks to its biocompatibility and ease of functionalization, has been demonstrated to be easily applicable as an antimicrobial agent, especially for the treatment of local infections.

Upper respiratory infections are some of the most common reasons for pediatric patients to present to the emergency department. A small percentage of these viral infections can evolve into acute bacterial sinusitis (ABS), which can be further complicated by the development of orbital, intracranial, and osseous complications. Differentiating between viral upper respiratory infections and ABS and identifying cases of ABS that require antibiotics can pose a challenge. This issue highlights the patterns of illness that are most consistent with ABS, based on the most current clinical practice guidelines. Additionally, this issue reviews clinical features that should raise suspicion for complicated disease and provides associated diagnostic and management pearls.

Emergence of antimicrobial-resistant bacteria (AMR) is one of the health major problems worldwide. The scientists are looking for a novel method to treat infectious diseases. Phage therapy is considered a suitable approach for treating infectious diseases. However, there are different challenges in this way. Some biological aspects can probably influence on therapeutic results and further investigations are necessary to reach a successful phage therapy. Bacteriophage activity can influence by bacterial defense system. Bacterial extracellular vesicles (BEVs) are one of the bacterial defense mechanisms which can modify the results of bacteriophage activity. BEVs have the significant roles in the gene transferring, invasion, escape, and spreading of bacteriophages. In this review, the defense mechanisms of bacteria against bacteriophages, especially BEVs secretion, the hidden linkage of BEVs and bacteriophages, and its possible consequences on the bacteriophage activity as well phage therapy will be discussed., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Phototherapy has become one of the most effective antibacterial methods due to its associated lack of drug resistance and its good antibacterial effect. For the purpose of avoiding the aggregation and premature release of photosensitive/photothermal agents during phototherapy, they can be mixed into three-dimensional hydrogels. The combination of hydrogels and phototherapy combines the merits of both hydrogels and phototherapy, overcomes the disadvantages of traditional antibacterial methodologies, and has broad application prospects. This review presents recent advancements in phototherapeutic antibacterial hydrogels including photodynamic antibacterial hydrogels, photothermal antibacterial hydrogels, photodynamic and photothermal synergistic antibacterial hydrogels, and other synergistic antibacterial hydrogels involving phototherapy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc) , Hemophilus influenzae , Mycobacterium abscessus ( Mab ), Pseudomonas aeruginosa , and Staphylococcus aureus . These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance. In this context, phage therapy, i.e., the use of phages, viruses that specifically infect bacteria, has become a promising strategy. In this review, we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Lower respiratory tract infections (LRTIs) present a significant global health burden, exacerbated by the rise in antimicrobial resistance (AMR). The persistence and evolution of multidrug-resistant bacteria intensifies the urgency for alternative treatments. This review explores bacteriophage (phage) therapy as an innovative solution to combat bacterial LRTIs. Phages, abundant in nature, demonstrate specificity towards bacteria, minimal eukaryotic toxicity, and the ability to penetrate and disrupt bacterial biofilms, offering a targeted approach to infection control. The article synthesises evidence from systematic literature reviews spanning 2000-2023, in vitro and in vivo studies, case reports and ongoing clinical trials. It highlights the synergistic potential of phage therapy with antibiotics, the immunophage synergy in animal models, and the pharmacodynamics and pharmacokinetics critical for clinical application. Despite promising results, the article acknowledges that phage therapy is at a nascent stage in clinical settings, the challenges of phage-resistant bacteria, and the lack of comprehensive cost-effectiveness studies. It stresses the need for further research to optimise phage therapy protocols and navigate the complexities of phage-host interactions, particularly in vulnerable populations such as the elderly and immunocompromised. We call for regulatory adjustments to facilitate the exploration of the long-term effects of phage therapy, aiming to incorporate this old-yet-new therapy into mainstream clinical practice to tackle the looming AMR crisis., Competing Interests: Conflict of interest: G. Ebrahimi and S. Rezvankhah are employees of Phageolytix Inc. A. Hashemi Shahraki and M. Mirsaeidi are shareholders of Phageolytix Inc. The other authors declare no conflict of interest., (Copyright ©The authors 2024.)

Bacteriophages (phages) are viruses specific to bacteria that target them with great efficiency and specificity. Phages were first studied for their antibacterial potential in the early twentieth century; however, their use was largely eclipsed by the popularity of antibiotics. Given the surge of antimicrobial-resistant strains worldwide, there has been a renaissance in harnessing phages as therapeutics once more. One of the key advantages of phages is their amenability to modification, allowing the generation of numerous derivatives optimised for specific functions depending on the modification. These enhanced derivatives could display higher infectivity, expanded host range or greater affinity to human tissues, where some bacterial species exert their pathogenesis. Despite this, there has been a noticeable discrepancy between the generation of derivatives in vitro and their clinical application in vivo. In most instances, phage therapy is only used on a compassionate-use basis, where all other treatment options have been exhausted. A lack of clinical trials and numerous regulatory hurdles hamper the progress of phage therapy and in turn, the engineered variants, in becoming widely used in the clinic. In this review, we outline the various types of modifications enacted upon phages and how these modifications contribute to their enhanced bactericidal function compared with wild-type phages. We also discuss the nascent progress of genetically modified phages in clinical trials along with the current issues these are confronted with, to validate it as a therapy in the clinic., (© 2024 The Author(s).)

Phage therapy has re-emerged as a promising treatment for non-resolving infections. Given the lack of approved phage treatments, there is a need to establish a compassionate use pipeline. Here, we present a protocol for phage matching, treatment, and monitoring for compassionate bacteriophage use in non-resolving infections. We describe steps for consultation and request implementation, evaluating and comparing different aspects of phage activity, and phage production. We then detail procedures for multidisciplinary meetings, ethics approvals, phage therapy, and follow-up. For complete details on the use and execution of this protocol, please refer to Onallah et al. 1 , 2 ., Competing Interests: Declaration of interests R.N.-P. has been a scientific consultant for BiomX and has participated and served as a PI and on Data Safety Monitoring Boards for a clinical trial by TechnoPhage., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Phage therapy holds much promise as an alternative to antibiotics for fighting infection. However, this approach is no panacea as recent results show that a small fraction of cells survives lytic phage infection due to both dormancy (i.e. formation of persister cells) and resistance (genetic change). In this brief review, we summarize evidence suggesting phages induce the persister state. Therefore, it is predicted that phage cocktails should be combined with antipersister compounds to eradicate bacterial infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacterial pathogens can infect a wide range of hosts and pose a threat to public and animal health as well as to agriculture. The emergence of antibiotic-resistant strains has increased this risk by making the treatment of bacterial infections even more challenging. Pathogenic bacteria thrive in various ecological niches, but they can also be specifically targeted and killed by bacteriophages (phages). Lytic phages are now investigated and even used, in some cases, as alternatives or complements to antibiotics for preventing or treating bacterial infections (phage therapy). As such, it is key to identify factors responsible for phage specificity and efficiency. Here, we review recent advances in virulence-associated factors that are targeted by phages. We highlight components of the bacterial cell surface, effector systems, and motility structures exploited by phages and the effects of phages on cell aggregation and communication. We also look at the fitness trade-off of phage resistance., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In contrast to the many reports of successful real-world cases of personalized bacteriophage therapy (BT), randomized controlled trials of non-personalized bacteriophage products have not produced the expected results. Here we present the outcomes of a retrospective observational analysis of the first 100 consecutive cases of personalized BT of difficult-to-treat infections facilitated by a Belgian consortium in 35 hospitals, 29 cities and 12 countries during the period from 1 January 2008 to 30 April 2022. We assessed how often personalized BT produced a positive clinical outcome (general efficacy) and performed a regression analysis to identify functional relationships. The most common indications were lower respiratory tract, skin and soft tissue, and bone infections, and involved combinations of 26 bacteriophages and 6 defined bacteriophage cocktails, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. In our dataset of 100 cases, eradication was 70% less probable when no concomitant antibiotics were used (odds ratio = 0.3; 95% confidence interval = 0.127-0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage-antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. We observed a combination of antibiotic re-sensitization and reduced virulence in bacteriophage-resistant bacterial isolates that emerged during BT. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. Fifteen adverse events were reported, including seven non-serious adverse drug reactions suspected to be linked to BT. While our analysis is limited by the uncontrolled nature of these data, it indicates that BT can be effective in combination with antibiotics and can inform the design of future controlled clinical trials. BT100 study, ClinicalTrials.gov registration: NCT05498363 ., (© 2024. The Author(s).)

Photothermal therapy (PTT) has emerged as a promising approach for treating bacterial infections. However, achieving a high photothermal conversion efficiency (PCE) of photothermal agents (PTAs) remains a challenge. Such a problem is usually compensated by the use of a high-intensity laser, which inevitably causes tissue damage. Here, we present a universal strategy to enhance PCE by regulating the molecular aggregation states of PTAs within thermoresponsive nanogels. We demonstrate the effectiveness of this approach using aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) PTAs, showing significant enhancements in PCE without the need for intricate molecular modifications. Notably, the highest PCEs reach up to 80.9% and 64.4% for AIE-NG and ACQ-NG, respectively, which are nearly 2-fold of their self-aggregate counterparts. Moreover, we elucidate the mechanism underlying PCE enhancement, highlighting the role of strong intermolecular π-π interactions facilitated by nanogel-induced volume contraction. Furthermore, we validate the safety and efficacy of this strategy in in vitro and in vivo models of bacterial infections at safe laser power densities, demonstrating its potential for clinical translation. Our findings offer a straightforward, universal, and versatile method to improve PTT outcomes while minimizing cytotoxicity, paving the way for enhanced treatment of bacterial infections with safe PTT protocols.

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing.

Hand infection is a rare complication in patients with diabetes. Its clinical outcomes depend on the severity of hand infection caused by bacteria, but the difference in bacterial species in the regional disparity is unknown. The purpose of this study was to explore the influence of tropical and nontropical regions on bacterial species and clinical outcomes for diabetic hand. A systematic literature review was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Moreover, the bacterial species and clinical outcomes were analyzed with respect to multicenter wound care in China (nontropical regions). Both mixed bacteria (31.2% vs. 16.6%, p = 0.014) and fungi (7.5% vs. 0.8%, p = 0.017) in the nontropical region were significantly more prevalent than those in the tropical region. Staphylococcus and Streptococcus spp. were dominant in gram-positive bacteria, and Klebsiella, Escherichia coli, Proteus and Pseudomonas in gram-negative bacteria occupied the next majority in the two regions. The rate of surgical treatment in the patients was 31.2% in the nontropical region, which was significantly higher than the 11.4% in the tropical region (p = 0.001). Although the overall mortality was not significantly different, there was a tendency to be increased in tropical regions (6.3%) compared with nontropical regions (0.9%). However, amputation (32.9% vs. 31.3%, p = 0.762) and disability (6.3% vs. 12.2%, p = 0.138) were not significantly different between the two regions. Similar numbers of cases were reported, and the most common bacteria were similar in tropical and nontropical regions in patients with diabetic hand. There were more species of bacteria in the nontropical region, and their distribution was basically similar, except for fungi, which had differences between the two regions. The present study also showed that surgical treatment and mortality were inversely correlated because delays in debridement and surgery can deteriorate deep infections, eventually leading to amputation and even death., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Over the years, the administration of antibiotics for the purpose of addressing bacterial infections has become increasingly challenging due to the increased prevalence of antimicrobial resistance exhibited by various strains of bacteria. Multidrug-resistant (MDR) bacterial species are rising due to the unavailability of novel antibiotics, leading to higher mortality rates. With these conditions, there is a need for alternatives in which phage therapy has made promising results. Phage-derived endolysins, phage cocktails, and bioengineered phages are effective and have antimicrobial properties against MDR and extensively drug-resistant strains. Despite these, it has been observed that phages can give antimicrobial activity to more than one bacterial species. Thus, phage cocktail against resistant strains provides broad spectrum treatment and magnitude of effectivity, which is many folds higher than antibiotics. Many commercially available endolysins such as Staphefekt SA.100, Exebacase (CF-301), and N-Rephasin®SAL200 are used in biofilm penetration and treating plant diseases. The role of CMP1 phage endolysin in transgenic tomato plants in preventing Clavibacter michiganensis infection and the effectiveness of phage in protecting Atlantic salmon from vibriosis have been reported. Furthermore, phage-derived endolysin therapy, such as TSPphg phage exogenous treatment, can aid in disrupting cell walls, leading to bacterial cell lysis. As animals in aquaculture and slaughterhouses are highly susceptible to bacterial infections, effective phage therapy instead of antibiotics can help treat poultry animals, preserve them, and facilitate disease-free trade. Using bioengineered phages and phage cocktails enhances the effectiveness by providing a broad spectrum of phages and target specificity. Research is currently being conducted on clinical trials to confirm the efficacy of engineered phages and phage cocktails in humans. Although obtaining commercial approval may be time-consuming, it will be beneficial in the postantibiotic era. This review provides an overview of the significance of phage therapy as a potential alternative to antibiotics in combating resistant bacterial strains and its application to various fields and emphasizes the importance of safeguarding and ensuring treatment efficacy., (© 2024 John Wiley & Sons Ltd.)

The nail unit is the most commonly affected area in hand infections, which can be primary infection or superinfection complicating other nail or skin disorders. Trauma, mechanical or chemical, is usually the trigger enabling infiltration of infectious organisms. Artificial nails and nail polish are also a possible cause of bacterial infection, harboring microorganisms. In severe acute bacterial infection, surgical intervention is often needed to prevent morbidity and disability. Abscess should always be drained, but viral infection such as herpetic whitlow, may mimic an abscess and, in contrast, requires non-operative treatment; to prevent sequelae. A more conservative approach is also generally advisable in less severe bacterial infection, other viral infections and in subacute or chronic nail infection. The present review deals with acute, subacute and chronic bacterial and viral infections of the nail unit, with a focus on diagnostic and treatment options. LEVEL OF EVIDENCE: III, systematic review of level III studies., (Copyright © 2022 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Phage therapy has recently attracted a great deal of attention to counteract the rapid emergence of antibiotic-resistant bacteria. In comparison to monophage therapy, phage cocktails are typically used to treat individual and/or multi-bacterial infections since the bacterial agents are unlikely to become resistant as a result of exposure to multiple phages simultaneously. The bacteriolytic effect of phage cocktails may produce efficient killing effect in comparison to individual phage. However, multiple use of phages (complex cocktails) may lead to undesirable side effects such as dysbiosis, horizontal gene transfer, phage resistance, cross resistance, and/or higher cost of production. Cocktail formulation, therefore, representa compromise between limiting the complexity of the cocktail and achieving substantial bacterial load reduction towards the targeted host organisms. Despite some constraints, the applications of monophage therapy have been well documented in the literature. However, phage cocktails-based approaches and their role for the control of pathogens have not been well investigated. In this review, we discuss the principle of phage cocktail formulations, their optimization strategies, major phage cocktail preparations, and their efficacy in inactivating various food borne bacterial pathogens.

Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to over-prescribing antibiotics. Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. Enzymes such as endolysins, exolysins, endopeptidases, endosialidases, and depolymerases produced by phages interact with bacterial surfaces, cell wall components, and exopolysaccharides, and may even destroy biofilms. Enzymatic cleavage of the host cell envelope components exposes specific receptors required for phage adhesion. Gram-positive bacteria are susceptible to phage infiltration through their peptidoglycan, cell wall teichoic acid (WTA), lipoteichoic acids (LTAs), and flagella. In Gram-negative bacteria, lipopolysaccharides (LPSs), pili, and capsules serve as targets. Defense mechanisms used by bacteria differ and include physical barriers (e.g., capsules) or endogenous mechanisms such as clustered regularly interspaced palindromic repeat (CRISPR)-associated protein (Cas) systems. Phage proteins stimulate immune responses against specific pathogens and improve antibiotic susceptibility. This review discusses the attachment of phages to bacterial cells, the penetration of bacterial cells, the use of phages in the treatment of bacterial infections, and the limitations of phage therapy. The therapeutic potential of phage-derived proteins and the impact that genomically engineered phages may have in the treatment of infections are summarized.

Bacteriophage therapy is a promising approach to treating bacterial infections. Research and development of bacteriophage therapy is intensifying due to the increase in antibiotic resistance and the faltering development of new antibiotics. Bacteriophage therapy uses bacteriophages (phages), i.e., prokaryotic viruses, to specifically target and kill pathogenic bacteria. The legal handling of this type of therapy raises several questions. These include whether phage therapeutics belong to a specially regulated class of medicinal products, and which legal framework should be followed with regard to the various technical ways in which phage therapeutics can be manufactured and administered. The article shows to which class of medicinal products phage therapeutics from wild type phages and from genetically modified (designer) phages do or do not belong. Furthermore, the article explains which legal framework is relevant for the manufacture and administration of phage therapeutics, which are manufactured in advance in a uniform, patient-independent manner, and for tailor-made patient-specific phage therapeutics. For the systematically coherent, successful translation of phage therapy, the article considers pharmaceutical law and related legal areas, such as genetic engineering law. Finally, the article shows how the planned legislative revisions of Directive 2001/83/EC and Regulation (EC) No 726/2004 may affect the legal future of phage therapy.

Objectives: Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized., Methods: Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central., Results: In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described., Conclusions: Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) using 2D nanomaterials (2DnMat) have recently emerged as promising alternative treatments for cancer and bacterial infections, both important global health challenges. The present review intends to provide not only a comprehensive overview, but also an integrative approach of the state-of-the-art knowledge on 2DnMat for PTT and MHT of cancer and infections. High surface area, high extinction coefficient in near-infra-red (NIR) region, responsiveness to external stimuli like magnetic fields, and the endless possibilities of surface functionalization, make 2DnMat ideal platforms for PTT and MHT. Most of these materials are biocompatible with mammalian cells, presenting some cytotoxicity against bacteria. However, each material must be comprehensively characterized physiochemically and biologically, since small variations can have significant biological impact. Highly efficient and selective in vitro and in vivo PTTs for the treatment of cancer and infections are reported, using a wide range of 2DnMat concentrations and incubation times. MHT is described to be more effective against bacterial infections than against cancer therapy. Despite the promising results attained, some challenges remain, such as improving 2DnMat conjugation with drugs, understanding their in vivo biodegradation, and refining the evaluation criteria to measure PTT or MHT effects., (© 2023 Wiley‐VCH GmbH.)

The steadily increasing number of drug-resistant bacterial species has prompted the search for alternative treatments, resulting in a growing interest in bacteriophages. Although they are viruses infecting bacterial cells, bacteriophages are an extremely important part of the human microbiota. By interacting with eukaryotic cells, they are able to modulate the functioning of many systems, including the immune and nervous systems, affecting not only the homeostasis of the organism, but potentially also the regulation of pathological processes. Therefore, the aim of this review is to answer the questions of (i) how animal/human immune systems respond to bacteriophages under physiological conditions and under conditions of reduced immunity, especially during bacterial infection; (ii) whether bacteriophages can induce negative changes in brain functioning after crossing the blood-brain barrier, which could result in various disorders or in an increase in the risk of neurodegenerative diseases; and (iii) how bacteriophages can modify gut microbiota. The crucial dilemma is whether administration of bacteriophages is always beneficial or rather if it may involve any risks.

Emergency clinicians frequently provide care to febrile infants aged ≤60 days in the emergency department. In these very young infants, fever may be the only presenting sign of invasive bacterial infection and, if untreated, invasive bacterial infection can lead to severe outcomes. This issue reviews newer risk-stratification tools and the 2021 American Academy of Pediatrics clinical practice guideline to provide recommendations for the evaluation and management of febrile young infants. The most recent literature assessing the risk of concomitant invasive bacterial infection with urinary tract infections or positive viral testing is also reviewed., (Copyright 2024 EB Medicine.)

Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages ( Salmonella phage SE&#95;SZW1, Acinetobacter phage AB&#95;SZ6, and Pseudomonas phage PA&#95;LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log 10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.IMPORTANCEPhage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes., Competing Interests: The authors declare no conflict of interest.

Objective: Optimization of the method of puncture treatment of acute bacterial maxillary sinusitis (ABMS) through the development of original devices for drainage of the maxillary sinus (MS)., Material and Methods: Registration and comparative analysis of the results of puncture methods of treatment of 120 patients with ABMS using developed new original devices for drainage of MS with one channels and with two channels in comparison with the Kulikovsky's needle (KN) was carried out. Based on the results of the analysis, the effectiveness of the original devices was assessed. During the clinical study, patients were divided into two groups: in group I, patients underwent of the MS puncture using KN, in group II, using original devices. Groups I and II, depending on the absence or presence of a block of the natural anastomosis MS, was divided into subgroups A and B, respectively. After puncture of the MS, the pain syndrome was assessed by patients using Visual Analogue Scale (VAS) and by doctors - using Touch Visual Pain (TVP) scale., Results: Our study showed that when puncturing the upper jaw with an original needle with one channels and with two channels, compared with the use of KN, there is a decrease in pain (the average VAS score was 1.5±0.3 and 1.7±0.3 points, respectively; the average TVP scale score was 0.9±0.2 and 1.8±0.3 points, respectively, the difference is significant, p ≤0.05). Patients of subgroup IB were manipulated with two KN, patients of subgroup IIB manipulated using the original device with two channels without an additional needle (the average VAS score was 3.0±0.4 and 1.3±0.3 points, respectively; the average TVP scale score was 2.7±0.4 and 1.0±0.2 points, respectively, the difference is significant, p ≤0.05). The doctors also assessed the devices used for puncture of the upper jaw. As a result of the study, the high efficiency and safety of using new original devices was established.

Phage therapy is an alternative approach to combat bacterial infections. In this approach, bacteriophages are used as antimicrobial agents due to their properties to infect specific bacterial cells, to propagate inside their hosts, and to lyse host cell to release progeny phages. However, to introduce bacteriophages to clinical or veterinary practice, it is necessary to construct a large library of precisely characterized phages. Therefore, in this chapter, methods for propagation, purification, and microbiological characterization of bacteriophages are presented in the light of their potential use in phage therapy. Isolation of newly discovered bacteriophages from different habitats is also described as it is a preliminary assessment of their efficacy in combating bacterial biofilms and in the treatment of bacterial infections in a simple insect model-Galleria mellonella., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aimed to provide a comprehensive overview of the current state of the literature on the therapeutical application of bacteriophages., Methods: First, a bibliometric analysis was performed using the database Web of Science to determine annual number of publications and citations. Second, a systematic literature review was conducted on randomized-controlled trials (RCTs) of phage therapy in PubMed., Results: Over the past decade, the number of publications on bacteriophage therapy increased more than fourfold with 212 articles in 2011 and 739 in 2022. The systematic search in PubMed yielded 7 RCTs eligible for inclusion, reporting on a total of 418 participants. Identified indications in this study included bacterial diarrhea, urinary tract infections, infected burn wounds, chronic otitis, chronic venous leg ulcers, and chronic rhinosinusitis. In three studies, mild to moderate adverse events were reported in 10/195 participants (5.1%). Three of the studies reported a statistically significant difference in outcomes comparing phage therapy with standard of care or placebo., Conclusion: Phage therapy has gained increasing interest over the years. RCTs on different indications suggest the safety of phage therapy; however, reasons why phage therapy is not yet well accepted are limitations in the study designs. For a successful translation into clinical practice researchers and clinicians should learn from the earlier experiences and consider issues such as the quality of phage preparation, sensitivity testing, titer and dosages, as well as access to the infection site and stability for standardized protocols and future trials., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

There is a strong rationale for using phages in patients with bone and joint infections (BJIs). Indeed, specific phages can infect and replicate in bacterial pathogens and have also demonstrated their activity in vitro against biofilm produced by different bacteria. However, there is a high variability of the different clinical forms of BJI, and their management is complex and frequently includes surgery followed by the administration of antibiotics. Regardless of the availability of active phages, optimal ways of phage administration in patients with BJIs are unknown. Otherwise, all BJIs are not relevant for phage therapy. Except for diabetic foot infection, a BJI with bone exposure is potentially not a relevant indication for phage therapy. On the counterpart, prosthetic joint infections in patients for whom a multidisciplinary expert team judges a conservative approach as the best option to keep the patient's function seem to be a relevant indication with the hypothesis that phage therapy could increase the rate of infection control. The ESCMID Study Group for Non-traditional Antibacterial Therapy (ESGNTA) was created in 2022. One century after the first use of phages as a therapy, the phage therapy 2.0 era, with the possibility to evaluate personalized phage therapy in modern medicine and orthopedic surgery, is just open., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The ESKAPE pathogens are the primary threat due to their constant spread of drug resistance worldwide. These pathogens are also regarded as opportunistic pathogens and could potentially cause nosocomial infections. Most of the ESKAPE pathogens have developed resistance to almost all the antibiotics that are used against them. Therefore, to deal with antimicrobial resistance, there is an urgent requirement for alternative non-antibiotic strategies to combat this rising issue of drug-resistant organisms. One of the promising alternatives to this scenario is implementing bacteriophage therapy. This under-explored mode of treatment in modern medicine has posed several concerns, such as preferable phages for the treatment, impact on the microbiome (or gut microflora), dose optimisation, safety, etc. The review will cover a rationale for phage therapy, clinical challenges, and propose phage therapy as an effective therapeutic against bacterial coinfections during pandemics. This review also addresses the expected uncertainties for administering the phage as a treatment against the ESKAPE pathogens and the advantages of using lytic phage over temperate, the immune response to phages, and phages in combinational therapies. The interaction between bacteria and bacteriophages in humans and countless animal models can also be used to design novel and futuristic therapeutics like personalised medicine or bacteriophages as anti-biofilm agents. Hence, this review explores different aspects of phage therapy and its potential to emerge as a frontline therapy against the ESKAPE bacterial pathogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)