Salphage: Salvage bacteriophage therapy for a chronic Enterococcus faecalis prosthetic joint infection

Doub, James B.; Johnson, Aaron J.

doi:10.1016/j.idcr.2023.e01854

Cited by 8 publications

(3 citation statements)

References 10 publications

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“…These are all as found in situ while treating infections caused by what are typically somewhat uncharacterized bacterial strains and, in many cases, also in combination with antibiotics [ 41 , 57 , 86 , 87 , 88 , 89 ], which can have antagonistic impacts on phage infection abilities [ 41 , 51 , 85 , 90 ]. In particular for the latter, note that of 18 clinical phage therapy studies that I was able to obtain—published in 2023 or, at the time of writing, which are published but still online ahead of print—at least 16 indicate treatments using phages in combination with antibiotics [ 57 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ]. See also [ 109 ], where 79 of the 114 clinical phage treatments reported “were administered in combination with standard-of-care antibiotics”.…”

Section: Discussionmentioning

confidence: 99%

Automating Predictive Phage Therapy Pharmacology

Abedon

2023

Antibiotics

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Viruses that infect as well as often kill bacteria are called bacteriophages, or phages. Because of their ability to act bactericidally, phages increasingly are being employed clinically as antibacterial agents, an infection-fighting strategy that has been in practice now for over one hundred years. As with antibacterial agents generally, the development as well as practice of this phage therapy can be aided via the application of various quantitative frameworks. Therefore, reviewed here are considerations of phage multiplicity of infection, bacterial likelihood of becoming adsorbed as a function of phage titers, bacterial susceptibility to phages also as a function of phage titers, and the use of Poisson distributions to predict phage impacts on bacteria. Considered in addition is the use of simulations that can take into account both phage and bacterial replication. These various approaches can be automated, i.e., by employing a number of online-available apps provided by the author, the use of which this review emphasizes. In short, the practice of phage therapy can be aided by various mathematical approaches whose implementation can be eased via online automation.

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Section: Discussionmentioning

confidence: 99%

Automating Predictive Phage Therapy Pharmacology

Abedon

2023

Antibiotics

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“…Phages have been shown to penetrate the extracellular polysaccharide (EPS) matrix of biofilms that antibiotics cannot and have been used to successfully disrupt biofilms of P. aeruginosa, Enterococcus faecalis, and Proteus mirabilis on various catheter devices [23][24][25]. In addition, phages have been used clinically to treat chronic biofilms of prosthetic joint infections by Staphylococcus epidermidis, methicillin-resistant S. aureus (MRSA), K. pneumoniae, and P. aeruginosa [8,[26][27][28].…”

Section: Options Againstmentioning

confidence: 99%

Combinations of Bacteriophage Are Efficacious against Multidrug-Resistant Pseudomonas aeruginosa and Enhance Sensitivity to Carbapenem Antibiotics

Kovacs,

Rapp,

Rankin

et al. 2024

Viruses

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The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge.

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“…Well tolerated in vivo [6][7][8][9][10], many phages possess antibiofilm properties [10][11][12], and many have been noted to work synergistically with antibiotics to eliminate biofilm infections [12,13]. However, there is ongoing uncertainty regarding the efficacy of phage therapy when applied in PJI cases; current reports have largely been confined to case reports [14][15][16] or small case series [17][18][19], and to the authors' knowledge, a summative analysis of in-human infection eradication rates after phage therapy application for PJI has not been performed. Despite this uncertainty, there is a need for larger, comparative studies, and there is now a phase 2 clinical trial underway to assess the therapeutic potential of phages for PJI management [20].…”

Section: Introductionmentioning

confidence: 99%

How Effective Is Phage Therapy for Prosthetic Joint Infections? A Preliminary Systematic Review and Proportional Meta-Analysis of Early Outcomes

Young,

Mehta,

Lee

et al. 2024

Medicina

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Background and Objectives: Despite the promise of phage therapy (PT), its efficacy in prosthetic joint infection (PJI) management is unknown. Much of the current literature is largely limited to case reports and series. Materials and Methods: In order to help inform power calculations for future clinical trials and comparative analyses, we performed a systematic review and proportional meta-analysis of early PT outcomes to provide a preliminary assessment of early phage therapy treatment outcomes for cases of PJI. Results: In a search of available literature across MEDLINE (Ovid, Wolters Kluwer, Alphen aan den Rijn, The Netherlands), Embase (Elsevier, Amsterdam, The Netherlands), the Web of Science Core Collection (Clarivate, London, UK), and Cochrane Central (Wiley, Hoboken, NJ, USA) up to 23 September 2023, we identified 37 patients with PJIs receiving adjunctive PT. Patients most frequently reported Staphylococcal species infection (95%) and intraarticular phage delivery (73%). Phage cocktail (65%) and antibiotic co-administration (97%) were common. A random-effects proportional meta-analysis suggested infection remission in 78% of patients (95% CI: 39%, 95%) (I2 = 55%, p = 0.08) and 83% with a minimum 12-month follow-up (95% CI: 53%, 95%) (I2 = 26%, p = 0.26). Conclusions: Our study provides a preliminary estimate of PT’s efficacy in PJIs and informs future comparative studies.

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Salphage: Salvage bacteriophage therapy for a chronic Enterococcus faecalis prosthetic joint infection

Cited by 8 publications

References 10 publications

Automating Predictive Phage Therapy Pharmacology

Automating Predictive Phage Therapy Pharmacology

Combinations of Bacteriophage Are Efficacious against Multidrug-Resistant Pseudomonas aeruginosa and Enhance Sensitivity to Carbapenem Antibiotics

How Effective Is Phage Therapy for Prosthetic Joint Infections? A Preliminary Systematic Review and Proportional Meta-Analysis of Early Outcomes

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