Implementation of a complex bone and joint infection phage therapy centre in France: lessons to be learned after 4 years' experience

Ferry, Tristan; Kolenda, Camille; Briot, Thomas; Lustig, Sébastien; Leboucher, Gilles; Laurent, Frédéric; Valour, Florent; Perpoint, Thomas; Ader, Florence; Roux, Sandrine; Becker, Agathe; Triffault-Fillit, Claire; Conrad, Anne; Pouderoux, Cécile; Chauvelot, Pierre; Chabert, Paul; Lippman, Johanna; Braun, E.; Servien, Elvire; Batailler, Cécile; Gunst, Stanislas; Schmidt, Axel; Sappey-Marinier, Eliott; Ode, Quentin; Fessy, Michel-Henry; Viste, Anthony; Besse, Jean-Luc; Chaudier, Philippe; Louboutin, Lucie; Haecke, Adrien Van; Mercier, Marcelle; Belgaïd, Vincent; Gazarian, Aram; Walch, A; Bertani, Antoine; Rongièras, Frédéric; Martres, Sébastien; Trouillet, Franck; Barrey, Cédric; Mojallal, Ali; Brosset, Sophie; Hanriat, Camille; Person, Hélène; Céruse, Philippe; Fuchsmann, Carine; Gleizal, A.; Aubrun, Frédéric; Dziadzko, Mikhail; Macabéo, Caroline; Patrascu, Dana; Beraud, Laëtitia; Roussel-Gaillard, Tiphaine; Dupieux, Céline; Josse, Jérôme; Craighero, Fabien; Boussel, L.; Pialat, Jean‐Baptiste; Morelec, I.; Tod, Michel; Gagnieu, Marie‐Claude; Goutelle, Sylvain; Mabrut, Eugénie; Medina, Mathieu; Laumay, Floriane; Bonhomme, Mélanie; Blazere, Leslie; Legendre, Tiphaine; Terrazzoni, Eline; Pirot, Fabrice; Merienne, Camille; Filali, Samira; Lapras, Benjamine

doi:10.1016/j.cmi.2021.09.027

Cited by 13 publications

(5 citation statements)

References 5 publications

(5 reference statements)

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“…The efficacy of PT has been documented in several case reports showing promising results both during topical and systemic applications. Phages have been used to treat surgical 3,4 and respiratory tract infections with MDR bacteria (reviewed in refs. [5][6][7], as well as recurrent bone and joint infections 8,9 , and an aortic graft infection due to MDR Pseudomonas aeruginosa 10 .…”

mentioning

confidence: 99%

Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa

Köhler,

Luscher,

Falconnet

et al. 2023

Nat Commun

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Bacteriophage therapy has been suggested as an alternative or complementary strategy for the treatment of multidrug resistant (MDR) bacterial infections. Here, we report the favourable clinical evolution of a 41-year-old male patient with a Kartagener syndrome complicated by a life-threatening chronic MDR Pseudomonas aeruginosa infection, who is treated successfully with iterative aerosolized phage treatments specifically directed against the patient’s isolate. We follow the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples. Phage titres in consecutive sputum samples indicate in patient phage replication. Phenotypic analysis and whole genome sequencing of sequential bacterial isolates reveals a clonal, but phenotypically diverse population of hypermutator strains. The MDR phenotype in the collected isolates is multifactorial and mainly due to spontaneous chromosomal mutations. All isolates recovered after phage treatment remain phage susceptible. These results demonstrate that clinically significant improvement is achievable by personalised phage therapy even in the absence of complete eradication of P. aeruginosa lung colonization.

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confidence: 99%

Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa

Köhler,

Luscher,

Falconnet

et al. 2023

Nat Commun

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“…This presents a financial challenge in taking phage therapy through the costly clinical trials system which is generally set up to meet the needs of sizeable businesses. Moreover, the provision of personalised treatments and phage for uncommon bacteria or niche clinical settings is unlikely to be financially attractive [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

The Safety and Efficacy of Phage Therapy: A Systematic Review of Clinical and Safety Trials

2022

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Trials of phage therapy have not consistently reported efficacy. This contrasts with promising efficacy rates from a sizeable and compelling body of observational literature. This systematic review explores the reasons why many phage trials have not demonstrated efficacy. Four electronic databases were systematically searched for safety and/or efficacy trials of phage therapy. Sixteen trials of phage therapy were included, in which 378 patients received phage. These were divided into historical (pre-2000; N = 3; n = 76) and modern (post-2000; N = 13; n = 302) trials. All 13 modern trials concluded that phage therapy was safe. Six of the 13 modern trials were exclusively safety trials. Seven modern trials investigated both safety and efficacy; efficacy was observed in two. Two of three historical trials did not comment on safety, while adverse effects in the third likely reflected the use of phage preparations contaminated with bacterial debris. None of the historical trials contained evidence of efficacy. The evidence from trials is that phage therapy is safe. For efficacy to be observed a therapeutic amount of the right phage(s) must be delivered to the right place to treat infections containing enough susceptible bacterial cells. Trials that have not demonstrated efficacy have not fulfilled one or more elements of this principle.

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“… 3 , 4 , 5 Pipelines for phage therapy are available in some places. 6 , 7 Nevertheless, due to the predominant personalized, compassionate basis, a standardized protocols for phage susceptibility testing and treatment are lacking. Such variability leads to significant variations in phage application in different locations and clinical indications.…”

Section: Before You Beginmentioning

confidence: 99%

Protocol for phage matching, treatment, and monitoring for compassionate bacteriophage use in non-resolving infections

Onallah,

Yerushalmy,

Braunstein

et al. 2024

STAR Protocols

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Implementation of a complex bone and joint infection phage therapy centre in France: lessons to be learned after 4 years' experience

Cited by 13 publications

References 5 publications

Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa

Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa

The Safety and Efficacy of Phage Therapy: A Systematic Review of Clinical and Safety Trials

Protocol for phage matching, treatment, and monitoring for compassionate bacteriophage use in non-resolving infections

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