Combining phages and antibiotic to enhance antibiofilm efficacy against an in vitro dual species wound biofilm

Akturk, Ergun; Melo, Luís D. R.; Oliveira, Hugo; Crabbé, Aurélie; Coenye, Tom; Azeredo, Joana

doi:10.1016/j.bioflm.2023.100147

Cited by 14 publications

(7 citation statements)

References 42 publications

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“…1.2 × 10 9 to 1 to 6 × 10 10 PFUs per patient). 26 , 39 , 41 In line with our study, Akturk et al 42 showed that gentamicin is an effective adjuvant of phage therapy against chronic wound infections, especially when applied simultaneously and repetitively, in a dual-species biofilm in vitro wound model. Moreover, several clinical studies from the Lyon Bone and Joint Study Group in France highlighted the use of phage therapy as an adjuvant to DAIR to salvage patients with relapsing S. aureus and Pseudomonas aeruginosa prosthetic knee infection.…”

Section: Discussionsupporting

confidence: 86%

Repetitive combined doses of bacteriophages and gentamicin protect against Staphylococcus aureus implant-related infections in Galleria mellonella

Mannala,

Rupp,

Walter

et al. 2024

Bone Joint Res

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AimsBacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella.MethodsFor the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses.ResultsIn the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models.ConclusionBased on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required.Cite this article: Bone Joint Res 2024;13(8):383–391.

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Section: Discussionsupporting

confidence: 86%

Repetitive combined doses of bacteriophages and gentamicin protect against Staphylococcus aureus implant-related infections in Galleria mellonella

Mannala,

Rupp,

Walter

et al. 2024

Bone Joint Res

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“…Another significant problem is the emergence of bacterial resistance during phage treatment, 13 especially after prolonged phage use [54]. A solution to this problem may be the use of bacteriophages together with antibiotics [36,55] or the use of a cocktail composed of several phages characterized by different mechanisms of action [37,45]. Access to phage therapy is limited.…”

Section: Problems and Challengesmentioning

confidence: 99%

The treatment of chronic wounds using bacteriophages

Bil,

Kiełbasa,

Kowalczyk

et al. 2024

J Educ Health Sport

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Introduction and aim of study: Chronic wounds are increasingly challenging global healthcare. These wounds, which take over 3 months to heal, are complicated by untreated infections and the formation of biofilm, hindering healing and antibiotic effectiveness. To tackle these issues, new treatments like bacteriophage therapy are being explored. Bacteriophages, viruses that target bacteria, offer promise in overcoming antibiotic resistance. However, their use presents challenges that need to be addressed. Material and methods: Our review is based on the analysis of materials collected in Pubmed, Elsevier and other scientific articles using keywords: “chronic wound”, “chronic wounds infection”, “biofilms”, “MDR”, “bacteriophage”, “phage therapy”. Conclusions: The rise of chronic wounds due to resistant infections poses a significant challenge for patients and healthcare systems. Multidrug-resistant bacteria, often forming biofilm, evade current treatments, urging the search for alternatives. Phage therapy, showing efficacy against various stubborn infections, including those from surgery or diabetes, gains attention. Advanced delivery systems enhance targeted treatment, while phage cocktails improve effectiveness, especially against multiple resistant strains. Safety is generally observed, but larger trials are needed. Though not a replacement for antibiotics, phage therapy offers hope, needing robust clinical validation. While challenges exist, its societal, commercial, and economic benefits suggest a promising future beyond clinical use.

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“…Con-sequently, there has been a growing interest in utilizing antibiotics as adjuncts to phage therapy in order to promote antibacterial outcomes. Moreover, researchers have undertaken both in vitro and in vivo studies, validating the antibiofilm efficacy of combining phages and antibiotics in refractory wound infections [113,114]. Additionally, the use of a "cocktail" phage therapy, which involves the combination of multiple phages with diverse mechanisms, has shown effectiveness in mitigating phage resistance.…”

Section: Perspectives and Challenges Of Phage Therapymentioning

confidence: 99%

Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections

Wang,

Du,

Dong

et al. 2024

IJMS

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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.

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Combining phages and antibiotic to enhance antibiofilm efficacy against an in vitro dual species wound biofilm

Cited by 14 publications

References 42 publications

Repetitive combined doses of bacteriophages and gentamicin protect against Staphylococcus aureus implant-related infections in Galleria mellonella

Repetitive combined doses of bacteriophages and gentamicin protect against Staphylococcus aureus implant-related infections in Galleria mellonella

The treatment of chronic wounds using bacteriophages

Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections

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