Efficacy Of Phage Therapy Research Articles

Inovirus-Encoded Peptides Induce Specific Toxicity in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a common opportunistic pathogen associated with nosocomial infections. The primary treatment for infections typically involves antibiotics, which can lead to the emergence of multidrug-resistant strains. Therefore, there is a pressing need for safe and effective alternative methods. Phage therapy stands out as a promising approach. However, filamentous prophages (Pfs) commonly found in P. aeruginosa encode genes with phage defense activity, thereby reducing the efficacy of phage therapy. Through a genomic analysis of the Pf4 prophage, we identified a 102 bp gene co-transcribed with the upstream gene responsible for phage release (zot gene), giving rise to a 33-amino-acid polypeptide that we have named Pf4-encoded toxic polypeptide (PftP4). The overexpression of PftP4 demonstrated cellular toxicity in P. aeruginosa, with subcellular localization indicating its presence in the cell membrane and a subsequent increase in membrane permeability. Notably, PftP4 homologues are found in multiple Pf phages and exhibit specificity in their toxicity towards P. aeruginosa among the tested bacterial strains. Our study reveals that the novel Pf-encoded polypeptide PftP4 has the potential to selectively target and eradicate P. aeruginosa, offering valuable insights for combating P. aeruginosa infections.

Phage-mediated virulence loss and antimicrobial susceptibility in carbapenem-resistant Klebsiella pneumoniae.

Bacteriophages, known for their ability to kill bacteria, are hampered in their effectiveness because bacteria are able to rapidly develop resistance, thereby posing a significant challenge for the efficacy of phage therapy. The impact of evolutionary trajectories on the long-term success of phage therapy remains largely unclear. Herein, we conducted evolutionary experiments, genomic analysis, and CRISPR-mediated gene editing, to illustrate the evolutionary trajectory occurring between phages and their hosts. Our results illustrate the ongoing "arms race" between a lytic phage and its host, a carbapenem-resistant Klebsiella pneumoniae clinical strain Kp2092, suggesting their respective evolutionary adaptations that shape the efficacy of phage therapy. Specifically, Kp2092 rapidly developed resistance to phages through mutations in a key phage receptor (galU) and bacterial membrane defenses such as LPS synthesis, however, this evolution coincides with unexpected benefits. Evolved bacterial clones not only exhibited increased sensitivity to clinically important antibiotics but also displayed a loss of virulence in an in-vivo model. In contrast, phages evolved under the selection pressure against Kp2092 mutants and exhibited enhanced bacterial killing potency, targeting mutations in phage tail proteins gp12 and gp17. These parallel evolutionary trajectories suggest a common genetic mechanism driving adaptation, ultimately favoring the efficacy of phage therapy. Overall, our findings highlight the potential of phages not only as agents for combating bacterial resistance, but also a driver of evolution outcomes that could lead to more favorable clinical outcomes in the treatment of multidrug resistance pathogens.IMPORTANCECarbapenem-resistant Klebsiella pneumoniae represents one of the leading pathogens for infectious diseases. With traditional antibiotics often being ineffective, phage therapy has emerged as a promising alternative. However, phage predation imposes a strong evolutionary pressure on the rapid evolution of bacteria, challenging treatment efficacy. Our findings illustrate how co-evolution enhances phage lytic capabilities through accumulated mutations in the tail proteins gp12 and gp17, while simultaneously reducing bacterial virulence and antibiotic resistance. These insights advance our understanding of phage-host interactions in clinical settings, potentially inspiring new approaches akin to an "arms race" model to combat multidrug-resistant crises effectively.

The Efficacy of Bacteriophage Therapy in Orthopaedic Field: A Systematic Review

INTRODUCTION: Bacterial infections are the cause of high mortality rates in the world. Antibiotics and multidrug work well together to treat the patient. The pathogens are harder to control and develop antibiotics resistance. In orthopaedic field, infections like osteomyelitis, septic arthritis, or infections of the bone, joints, or implants (periprosthetic joint infections [PJI]) can be difficult to resolve both microbiologically and clinically. Bacterial viruses (bacteriophages) are one possible substitute. Due to their great host specificity, lack of adverse effects, and safety for eukaryotic cells, these viruses provide novel advantages, such as the safe treatment of illnesses. MATERIAL AND METHODS: Three databases were used for the bibliographical search: Google Scholar, PubMed, and ScienceDirect for case report related to bacteriophage therapy and antibiotic resistance in orthopaedics, which were published between 2014 and 2024, which based on PRISMA guidelines qualified 10 articles for systematic review. RESULT: In orthopaedic cases biofilm formation is widely recognized as the main obstacle to effective prevention and treatment. Biofilm production is intimately related to bacteria's capacity to create chronic illnesses and the challenge of overcoming them. The biofilm-disrupting properties of certain phages make them a promising option for managing device-associated infections. The capacity of phages to enter a biofilm and then cling to the surface of the host bacteria to infect and lyse it. The effectiveness of the reticuloendothelial system's clearance and possibly the production of phage-specific antibodies, which could result in phage inactivation, determine how long phages stay in systemic therapy. CONCLUSION: Bacteriophages is a safe and effective treatment option, regardless of whether it is used alone or in conjunction with antibiotics and/or surgery. Bacteriophages is particularly well-suited for inclusion in multidimensional strategies to address infections due to its adaptability and versatility. Rather than replacing antibiotics, Bacteriophages should complement their effects to enhance infection management. Keywords: Bacteriophages, Phage Therapy, Antibiotic Resistance, Orthopaedic, Biofilm

Effects of Oral Application of Bacteriophage Cocktails to Treat Aeromoniasis Caused by Aeromonas hydrophila

Aeromonas hydrophila is a prominent pathogen of freshwater fish. Antimicrobials can be used to treat Motile Aeromonas septicemia (MAS) caused by A. hydrophila. However, bacteria may become resistant to these drugs, and antimicrobials could pollute water. Innovative eco-friendly approaches must be developed to avoid and address MAS. The present study used bacteriophage cocktails to treat rainbow trout infected with MAS. Fish were administered an oral cocktail of Aquaneticvirus APT65, AP-Y28, AP-T5, and AP-ATCC phages to evaluate the therapeutic efficacy of phage therapy against A. hydrophila-induced fish mortality. The survival of Aquaneticvirus APT65 phage in fish organs was also evaluated over an 8-day study period. Aquaneticvirus APT65 phage was found in fish internal organs, demonstrating that the phage may cross the intestinal barrier. In challenge trials with the LD70 dosa of A. hydrophila, phage cocktail doses of lx108 PFU/g feed reduced mortality in rainbow trout by 32-44.8%. Phage treatment prior to infection significantly increased fish survival compared to treatment after one day of infection. Relative percent survival results showed that oral phage cocktails protected fish against A. hydrophila mortality in a time-dependent way. This study is valuable for fanner-level application because it includes simple, practical procedures for phage cocktail formulation, medicated feed preparation, and oral administration, as well as data on phage survival and protection data.

Bacteriophage Therapy as a Promising Alternative for Antibiotic-Resistant Enterococcus faecium: Advances and Challenges.

Enterococcus faecium is a Gram-positive bacterium increasingly identified as a critical nosocomial pathogen that poses significant treatment challenges due to its resistance to multiple antibiotics, particularly vancomycin-resistant E. faecium (VRE) strains. The urgent need for alternative therapeutic strategies has renewed interest in bacteriophage (phage) therapy, given phages specificity and bactericidal potential. This review explores the advancements in phage therapy against antibiotic-resistant E. faecium, including phage morphological diversity, genomic characteristics, and infection mechanisms. The efficacy of phage therapy in in vitro, ex vivo, and in vivo models and the compassionate use in clinical settings are evaluated, highlighting the promising outcomes of phage-antibiotic synergies and biofilm disruption. Key challenges and future research directions are discussed, with a focus on improving therapeutic efficacy and overcoming bacterial resistance. This review emphasizes the potential of phage therapy as a viable solution for managing multidrug-resistant E. faecium infections and underscores the importance of future investigations to enhance clinical applications.

Metapopulation model of phage therapy of an acute Pseudomonas aeruginosa lung infection.

Phage therapy is increasingly employed as a compassionate treatment for severe infections caused by multidrug-resistant (MDR) bacteria. However, the mixed outcomes observed in larger clinical studies highlight a gap in understanding when phage therapy succeeds or fails. Previous research from our team, using in vivo experiments and single-compartment mathematical models, demonstrated the synergistic clearance of acute P. aeruginosa pneumonia by phage and neutrophils despite the emergence of phage-resistant bacteria. In fact, the lung environment is highly structured, prompting the question of whether immunophage synergy explains the curative treatment of P. aeruginosa when incorporating realistic physical connectivity. To address this, we developed a metapopulation network model mimicking the lung branching structure to assess phage therapy efficacy for MDR P. aeruginosa pneumonia. The model predicts the synergistic elimination of P. aeruginosa by phage and neutrophils but emphasizes potential challenges in spatially structured environments, suggesting that higher innate immune levels may be required for successful bacterial clearance. Model simulations reveal a spatial pattern in pathogen clearance where P. aeruginosa are cleared faster at distal nodes of the bronchial tree than in primary nodes. Interestingly, image analysis of infected mice reveals a concordant and statistically significant pattern: infection intensity clears in the bottom before the top of the lungs. The combined use of modeling and image analysis supports the application of phage therapy for acute P. aeruginosa pneumonia while emphasizing potential challenges to curative success in spatially structured in vivo environments, including impaired innate immune responses and reduced phage efficacy.

Phage-specific antibodies: are they a hurdle for the success of phage therapy?

Phage therapy has attracted attention again owing to the increasing number of drug-resistant bacteria. Although the efficacy of phage therapy has been reported, numerous studies have indicated that the generation of phage-specific antibodies resulting from phage administration might have an impact on clinical outcomes. Phage-specific antibodies promote phage uptake by macrophages and contribute to their rapid clearance from the body. In addition, phage-specific neutralizing antibodies bind to the phages and diminish their antibacterial activity. Thus, phage-specific antibody production and its role in phage therapy have been analyzed both in vitro and in vivo. Strategies for prolonging the blood circulation time of phages have also been investigated. However, despite these efforts, the results of clinical trials are still inconsistent, and a consensus on whether phage-specific antibodies influence clinical outcomes has not yet been reached. In this review, we summarize the phage-specific antibody production during phage therapy. In addition, we introduce recently performed clinical trials and discuss whether phage-specific antibodies affect clinical outcomes and what we can do to further improve phage therapy regimens.

Zebrafish as an effective model for evaluating phage therapy in bacterial infections: a promising strategy against human pathogens.

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.

Optimized Dosing and Delivery of Bacteriophage Therapy for Wound Infections.

Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistant Pseudomonas aeruginosa. However, the optimal dosing and delivery strategies for phage therapy remain unclear. In a mouse wound infection model, we investigated the impact of dose, frequency, and administration route on the efficacy of phage therapy. We find that topical but not intravenous delivery is effective in this model. High-doses of phage reduces bacterial burden more effectively than low-doses, and repeated dosing achieves the highest eradication rates. Building on these insights, we developed "HydroPhage", a hyaluronan-based hydrogel system that uses dynamic covalent crosslinking to deliver high-titre phages over one week. HydroPhage eradicates infections five times more effectively than intravenous injection. We conclude that hydrogel-based sustained phage delivery enhances the efficacy of phage therapy and offers a practical, well-tolerated option for topical application.

Quorum sensing positively regulates CPS-dependent Autographiviridae phage infection in Vibrio alginolyticus.

Phage resistance is a direct threat to phage therapy, and understanding phage-host interactions, especially how bacteria block phage infection, is essential for developing successful phage therapy. In the present study, we demonstrate for the first time that Vibrio alginolyticus uses quorum sensing (QS) to promote capsular polysaccharide (CPS)-specific phage infection by upregulating ugd expression, which is necessary for the synthesis of Autographiviridae phage receptor CPS. Although increased CPS-specific phage susceptibility is a novel trade-off mediated by QS, it results in the upregulation of virulence factors, promoting biofilm development and enhanced capsular polysaccharide production in V. alginolyticus. This suggests that inhibiting QS may improve the effectiveness of antibiotic treatment, but it may also reduce the efficacy of phage therapy.

Bacteriophage therapy and infective endocarditis - is itrealistic?

Infective endocarditis (IE) is a severe infection of the inner heart. Even with current standard treatment, the mean in-hospital mortality is as high as 15-20%, and 1-year mortality is up to 40% for left-sided IE. Importantly, IE mortality rates have not changed substantially over the past 30 years, and the incidence of IE is rising. The treatment is challenging due to the bacterial biofilm mode of growth inside the heart valve vegetations, resulting in antibiotic tolerance. Achieving sufficient antibiotic anti-biofilm concentrations in the biofilms of the heart valve vegetations is problematic, even with high-dose and long-term antibiotic therapy. The increasing prevalence of IE caused by antibiotic-resistant bacteria adds to the challenge. Therefore, adjunctive antibiotic-potentiating drug candidates and strategies are increasingly being investigated. Bacteriophage therapy is a reemerging antibacterial treatment strategy for difficult-to-treat infections, mainly biofilm-associated and caused by multidrug-resistant bacteria. However, significant knowledge gaps regarding the safety and efficacy of phage therapy impede more widespread implementation in clinical practice. Hopefully, future preclinical and clinical testing will reveal whether it is a viable treatment. The objective of the present review is to assess whether bacteriophage therapy is a realistic treatment for IE.

Phage therapy for intracellular MRSA infections and navigating transduction risks

In response to escalating antibiotic resistance, Methicillin-resistant Staphylococcus aureus (MRSA) infections, especially chronic intracellular cases, pose a persistent challenge. Phage therapy offers a promising alternative, targeting intracellular MRSA effectively. This review explores phage therapy's mechanisms, efficacy, challenges, and future prospects, with a focus on transduction risks. The review details phage therapy's intricate mechanisms against MRSA, highlighting dynamic phage-bacterial interactions within host cells. Evidence and case studies underscore transduction risks, including genetic element transfer and antibiotic resistance acquisition. Studies demonstrating phage therapy's efficacy against intracellular MRSA stress the need for tailored strategies and innovative approaches for enhanced phage access and efficacy within cells. Challenges like phage resistance and cell penetration limitations are examined, with proposed solutions to improve intracellular phage activity. Cutting-edge technologies such as whole-genome sequencing and single-cell analysis are discussed for monitoring and controlling transduction events. Collaboration among researchers, healthcare professionals, and regulators is emphasized to establish robust guidelines and address biosecurity concerns in phage therapy applications.

Isolation and characterisation of Pseudomonas aeruginosa bacteriophage isolated from Batu Pahat, Johor, Malaysia

The World Health Organization has classified Pseudomonas aeruginosa as a 'Priority One and Critical Pathogen' for which research and design of new antibiotics are urgently needed due to its high rate of antimicrobial resistance. Phage therapy, which uses bacteriophages (phages), has been proposed as an antibacterial agent and shows potential for combating this issue. This study aimed to isolate and characterise bacteriophages from different environmental samples that act specifically against P. aeruginosa. The phages were tested to determine their ability to lyse P. aeruginosa using a spot test. Transmission electron microscopy (TEM) was employed to determine the structure, size and phage family, while specificity and sensitivity tests were conducted using six different bacterial species and 20 clinical multi-drug resistant P. aeruginosa isolates, respectively. Phage PA1 was isolated from Batu Pahat, Johor and using a spot test, PA1 could form clear plaques against P. aeruginosa. PA1 was present in a high titer of 1.06 (± 32.2) x 1010 PFUs/ml. Based on TEM analysis, PA1 was classified as a member of the Myoviridae family. Host-range analysis displayed that PA1 had 100% specificity towards P. aeruginosa and only 45% sensitivity towards different P. aeruginosa clinical isolates. Phage PA1 demonstrated lysis of P. aeruginosa but exhibited a narrow host range, presenting a challenge for phage therapy. A promising approach to overcome this limitation involves using phage cocktails containing multiple strains of phages to broaden the host range and enhance the overall efficacy of phage therapy.

Phage K exposure generates phage-neutralizing activity in a rabbit model-humoral receptiveness may impact efficacy of phage therapy.

Phage therapy has not been established in the clinical routine, in part due to uncertainties concerning efficacy and immunogenicity. Here, three rabbits were immunized against staphylococcal phage K to assess viral potency in the presence of immunized serum. Three rabbits received weekly intramuscular injections of ~1010±1 pfu/mL phage K. Phage K-specific IgG formation was measured by an enzyme-linked immunosorbent assay (ELISA); phage inactivation was assessed by calculating K-rates. Using transmission electron microscopy (TEM) and immunogold labeling, antibody binding to phage K was visualized. This was numerically assessed by objective imaging analysis comparing the relative distances of each gold particle to the nearest phage head and tail structure. Immunization led to a strong IgG response, plateauing 7 days after the last phage injection. There was no significant correlation between K-rate and antibody titer over time. TEM showed IgG binding to the head structure of phage K. Image analysis showed a significant reduction in relative distances between antibodies and phage head structures when comparing samples from day 0 and day 28 (P < 0.0001). These results suggest that while individual serum analysis for antibodies against therapeutic phage bears consideration prior to and with prolonged therapy, during phage application, the formation of specific antibodies against phage may only partially explain decreased phage potency in the presence of immunized serum. Instead, other factors may contribute to an individual's "humoral receptiveness" to phage therapy. Future investigations should be directed toward the identification of the humoral factors that have the most significant predictive value on phage potency in vivo.

Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application.

The treatment of musculoskeletal infections (MSIs), including periprosthetic joint infection (PJI) and fracture-related infection (FRI), is often complicated by biofilm-related challenges necessitating multiple revision surgeries and incurring substantial costs. The emergence of antimicrobial resistance (AMR) adds to the complexity of the problem, leading to increased morbidity and healthcare expenses. There is an urgent need for novel antibacterial strategies, with the World Health Organization endorsing non-traditional approaches like bacteriophage (phage) therapy. Phage therapy, involving the targeted application of lytic potent phages, shows promise in the treatment of MSIs. Although historical clinical trials and recent case studies present significant milestones in the evolution of phage therapy over the past century, challenges persist, including variability in study designs, administration protocols and phage selection. Efforts to enhance treatment efficacy consist of personalized phage therapy and combination with antibiotics. Future perspectives entail addressing regulatory barriers, standardizing treatment protocols, and conducting high-quality clinical trials to establish phage therapy's efficacy for the treatment of MSIs. Initiatives like the PHAGEFORCE study and the PHAGEinLYON Clinic programme aim to streamline phage therapy, facilitating personalized treatment approaches and systematic data collection to advance its clinical utility in these challenging infections.

Targeting Superbugs: Efficacy of Bacteriophage Therapy against Antibiotic-Resistant Pseudomonas Aeruginosa in Urinary Tract Infections

The rise of antibiotic-resistant bacterial infections poses a significant challenge to global health, particularly in the treatment of urinary tract infections (UTIs). This study evaluates the potential of bacteriophage therapy as an alternative treatment against antibiotic-resistant Pseudomonas Aeruginosa isolated from UTI samples. We isolated 12 strains of P. aeruginosa from 50 UTI samples and conducted extensive antibiotic susceptibility testing, revealing significant resistance to multiple conventional antibiotics such as Tetracycline, Septran, Ceftazidime, and Cefepime, while showing susceptibility to Imipenem and Meropenem. Concurrently, we isolated and characterized bacteriophages from sewage samples that demonstrated specific lytic activity against the antibiotic-resistant strains. Our findings suggest that bacteriophage therapy provides a high specificity and efficacy in targeting antibiotic-resistant P. aeruginosa, offering a promising alternative to traditional antibiotic therapies. This study underscores the potential of phages in clinical applications, advocating for further clinical trials and the development of a regulatory framework to integrate phage therapy into mainstream medical practice for combating antibioticresistant infections.

The rise, fall, and resurgence of phage therapy for urinary tract infection.

In the face of rising antimicrobial resistance, bacteriophage therapy, also known as phage therapy, is seeing a resurgence as a potential treatment for bacterial infections including urinary tract infection (UTI). Primarily caused by uropathogenic Escherichia coli, the 400 million UTI cases annually are major global healthcare burdens and a primary cause of antibiotic prescriptions in the outpatient setting. Phage therapy has several potential advantages over antibiotics including the ability to disrupt bacterial biofilms and synergize with antimicrobial treatments with minimal side effects or impacts on the microbiota. Phage therapy for UTI treatment has shown generally favorable results in recent animal models and human case reports. Ongoing clinical trials seek to understand the efficacy of phage therapy in individuals with asymptomatic bacteriuria and uncomplicated cystitis. A possible challenge for phage therapy is the development of phage resistance in bacteria during treatment. While resistance frequently develops in vitro and in vivo, resistance can come with negative consequences for the bacteria, leaving them susceptible to antibiotics and other environmental conditions and reducing their overall virulence. "Steering" bacteria toward phage resistance outcomes that leave them less fit or virulent is especially useful in the context of UTI where poorly adherent or slow-growing bacteria are likely to be flushed from the system. In this article, we describe the history of phage therapy in treating UTI and its current resurgence, the state of its clinical use, and an outlook on how well-designed phage therapy could be used to "steer" bacteria toward less virulent and antimicrobial-susceptible states.

Prospects and Challenges of Bacteriophage Substitution for Antibiotics in Livestock and Poultry Production.

The overuse and misuse of antibiotics in the livestock and poultry industry has led to the development of multi-drug resistance in animal pathogens, and antibiotic resistance genes (ARGs) in bacteria transfer from animals to humans through the consumption of animal products, posing a serious threat to human health. Therefore, the use of antibiotics in livestock production has been strictly controlled. As a result, bacteriophages have attracted increasing research interest as antibiotic alternatives, since they are natural invaders of bacteria. Numerous studies have shown that dietary bacteriophage supplementation could regulate intestinal microbial composition, enhance mucosal immunity and the physical barrier function of the intestinal tract, and play an important role in maintaining intestinal microecological stability and normal body development of animals. The effect of bacteriophages used in animals is influenced by factors such as species, dose, and duration. However, as a category of mobile genetic elements, the high frequency of gene exchange of bacteriophages also poses risks of transmitting ARGs among bacteria. Hence, we summarized the mechanism and efficacy of bacteriophage therapy, and highlighted the feasibility and challenges of bacteriophage utilization in farm animal production, aiming to provide a reference for the safe and effective application of bacteriophages as an antibiotic alternative in livestock and poultry.

Long-Term Effectiveness of Engineered T7 Phages Armed with Silver Nanoparticles Against Escherichia coli Biofilm.

The escalating threat of antibiotic-resistant bacteria, particularly those forming biofilm structures, underscores the urgent need for alternative treatment strategies. Bacteriophages have emerged as promising agents for combating bacterial infections, especially those associated with biofilm formation. However, the efficacy of phage therapy can be limited by the development of bacterial resistance and biofilm regrowth. Interestingly, phages could be combined with other agents, such as metal nanoparticles, to enhance their antibacterial effectiveness. Since the therapeutic strategy of using phages and metal nanoparticles has been developed relatively recently, evaluating its efficacy under various conditions is essential, with a particular focus on the duration of activity. This study tested the hypothesis that a novel approach to combating bacterial biofilms, based on phages armed with silver nanoparticles (AgNPs), would exhibit enhanced activity over an extended period after application. In this work, we investigated the potential of engineered T7 phages armed with AgNPs for eradicating Escherichia coli biofilm. We demonstrated that such biomaterial exhibits sustained antimicrobial activity even after prolonged exposure. Compared to phages alone or AgNPs alone, the biomaterial significantly enhances biofilm eradication, particularly after 48hours of treatment. These findings highlight the potential of synergistic phage-nanoparticle strategies for combatting biofilm-associated infections.

The Safety and Efficacy of Phage Therapy for Infections in Cardiac and Peripheral Vascular Surgery: A Systematic Review.

New approaches to managing infections in cardiac and peripheral vascular surgery are required to reduce costs to patients and healthcare providers. Bacteriophage (phage) therapy is a promising antimicrobial approach that has been recommended for consideration in antibiotic refractory cases. We systematically reviewed the clinical evidence for phage therapy in vascular surgery to support the unlicensed use of phage therapy and inform future research. Three electronic databases were searched for articles that reported primary data about human phage therapy for infections in cardiac or peripheral vascular surgery. Fourteen reports were eligible for inclusion, representing 40 patients, among which an estimated 70.3% of patients (n = 26/37) achieved clinical resolution. A further 10.8% (n = 4/37) of patients showed improvement and 18.9% (n = 7/37) showed no improvement. Six of the twelve reports that commented on the safety of phage therapy did not report adverse effects. No adverse effects documented in the remaining six reports were directly linked to phages but reflected the presence of manufacturing contaminants or release of bacterial debris following bacterial lysis. The reports identified by this review suggest that appropriately purified phages represent a safe and efficacious treatment option for infections in cardiac and peripheral vascular surgery.