Proportion of patients with prosthetic joint infection eligible for adjuvant phage therapy: a French single-centre retrospective study.

BACKGROUND: Bone and joint infections represent a major public health issue due to their increasing prevalence, their functional prognosis and their cost to society. Phage therapy has valuable anti-biofilm properties against prosthetic joint infections (PJI). The aim of this study was to establish the proportion of patients eligible for phage therapy and to assess their clinical outcome judged against all patients presenting with PJI. METHOD: . Patients admitted for periprosthetic joint infection (PJI) at a French general hospital between 2015 and 2019 were retrospectively included. Eligibility for phage therapy was determined based on French recommendations, with polymicrobial infections serving as exclusion criteria. Patients were categorized into two groups: those eligible and those ineligible for phage therapy. We analyzed their characteristics and outcomes, including severe adverse events, duration of intravenous antibiotic therapy, length of hospitalization, and relapse rates. RESULTS: . In this study, 96 patients with PJI were considered in multidisciplinary medical meetings. Of these, 44% patients (42/96) were eligible for additional phage therapy. This group of patients had a longer duration of intravenous therapy (17 days vs. 10 days, p = 0.02), more severe adverse events (11 vs. 3, p = 0.08) and had a longer hospital stay (43 days vs. 18 days, p < 0.01). CONCLUSION: . A large number of patients met eligibility criteria for phage therapy and treatment and follow-up is more complex. A larger epidemiological study would more accurately describe the prognosis of eligible patients.

Quality and safety requirements for sustainable phage therapy products.

The worldwide antibiotic crisis has led to a renewed interest in phage therapy. Since time immemorial phages control bacterial populations on Earth. Potent lytic phages against bacterial pathogens can be isolated from the environment or selected from a collection in a matter of days. In addition, phages have the capacity to rapidly overcome bacterial resistances, which will inevitably emerge. To maximally exploit these advantage phages have over conventional drugs such as antibiotics, it is important that sustainable phage products are not submitted to the conventional long medicinal product development and licensing pathway. There is a need for an adapted framework, including realistic production and quality and safety requirements, that allows a timely supplying of phage therapy products for 'personalized therapy' or for public health or medical emergencies. This paper enumerates all phage therapy product related quality and safety risks known to the authors, as well as the tests that can be performed to minimize these risks, only to the extent needed to protect the patients and to allow and advance responsible phage therapy and research.

A Century of Clinical Use of Phages: A Literature Review.

Growing antibiotic resistance and the broken antibiotic market have renewed interest in the use of phages, a century-old therapy that fell into oblivion in the West after two decades of promising results. This literature review with a particular focus on French literature aims to complement current scientific databases with medical and non-medical publications on the clinical use of phages. While several cases of successful treatment with phages have been reported, prospective randomized clinical trials are needed to confirm the efficacy of this therapy.

Benefits of Combined Phage-Antibiotic Therapy for the Control of Antibiotic-Resistant Bacteria: A Literature Review.

With the increase in bacterial resistance to antibiotics, more and more therapeutic failures are being reported worldwide. The market for antibiotics is now broken due to the high cost of developing new molecules. A promising solution to bacterial resistance is combined phage-antibiotic therapy, a century-old method that can potentiate existing antibiotics by prolonging or even restoring their activity against specific bacteria. The aim of this literature review was to provide an overview of different phage-antibiotic combinations and to describe the possible mechanisms of phage-antibiotic synergy.

Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections.

The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy.

The epic of phage therapy.

The present report describes the presentation given by Dr Alain Dublanchet at the Stanier/Oxford Hygiene Symposium, held in Oxford, England, on November 10, 2004. Dr Dublanchet's lecture, entitled 'The epic of phage therapy', provided a sequential account of the use of phage as an antimicrobial from its discovery to its rise and fall and current rediscovery.