Considerations for the Use of Phage Therapy in Clinical Practice

Suh, Gina A.; Lodise, Thomas; Tamma, Pranita D.; Knisely, Jane M.; Alexander, José; Aslam, Saima; Barton, Karen D.; Bizzell, Erica; Totten, Katherine M. C.; Campbell, Joseph L.; Chan, Benjamin K; Cunningham, Scott A.; Goodman, Katherine E; Greenwood‐Quaintance, Kerryl E.; Harris, Anthony D.; Hesse, Shayla; Maresso, Anthony W.; Nussenblatt, Véronique; Pride, David T.; Rybak, Michael J.; Sund, Zoë; Duin, David van; Tyne, Daria Van; Patel, Robin

doi:10.1128/aac.02071-21

Cited by 230 publications

(199 citation statements)

References 192 publications

(371 reference statements)

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“…(1) Patient's request for phage therapy: A physician trained in phage biology will discuss the risks, in general, as well as possible side effects in detail, and chances of success of phage therapy in a calm atmosphere [34]. Possible misinformation or misunderstandings are addressed in a friendly manner, and the adjuvant nature of most phage therapies is explained.…”

Section: Overviewmentioning

confidence: 99%

“…(3) Logistics: Logistics combining the different competencies required for phage therapy should be assessed and optimized as indicated in this manuscript. Particularly, the following resources should be available: The adequacy of the logistics needs to be assessed before phage therapy preparation begins [34,36].…”

Section: Overviewmentioning

confidence: 99%

“…This individual consent form addresses the patient's individual circumstances and clearly outlines the phage therapy procedure, potential complications, and alternative treatment options. All co-morbidities, pre-existing conditions, allergies, and medication are considered [34].…”

Section: Overviewmentioning

confidence: 99%

“…Transmission electron microscopy can provide additional information; however, it is not mandatory prior to phage therapy [11,34,47]. The phage laboratory personnel might be trained in further methods, such as ultracentrifugation, dialysis, biofilm formation, and flow analysis.…”

Section: Guideline No 2: Properties Of the Phage Laboratory And Labor...mentioning

confidence: 99%

“…Responsible: sequencing laboratory Genetic safety testing, based on the viral sequence, is performed by an expert laboratory on phage genetics, considering the following aspects [11,12,17,34,[47][48][49] Predicting the suitability of phages for patients can be challenging, and it requires a high level of expertise.…”

Section: Guideline No 3: Genetic Safety Checkmentioning

confidence: 99%

See 4 more Smart Citations

Practical Assessment of an Interdisciplinary Bacteriophage Delivery Pipeline for Personalized Therapy of Gram-Negative Bacterial Infections

et al. 2022

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Despite numerous advances in personalized phage therapy, smooth logistics are challenging, particularly for multidrug-resistant Gram-negative bacterial infections requiring high numbers of specific lytic phages. We conducted this study to pave the way for efficient logistics for critically ill patients by (1) closely examining and improving a current pipeline under realistic conditions, (2) offering guidelines for each step, leading to safe and high-quality phage supplies, and (3) providing a tool to evaluate the pipeline’s efficiency. Due to varying stipulations for quality and safety in different countries, we focused the pipeline on all steps up to a required phage product by a cell-free extract system. The first of three study runs included patients with respiratory bacterial infections from four intensive care units, and it revealed a cumulative time of up to 23 days. Ultimately, adjustment of specific set points of the vulnerable components of the pipeline, phage isolation, and titration increased the pipeline’s efficiency by 15% and decreased the maximum required time to 13 days. We present a site-independent practical approach to establish and optimize pipelines for personalized phage delivery, the co-organization of pipeline components between different institutions, non-binding guidelines for every step, and an efficiency check for phage laboratories.

show abstract

Section: Overviewmentioning

confidence: 99%

Section: Overviewmentioning

confidence: 99%

Section: Overviewmentioning

confidence: 99%

Section: Guideline No 2: Properties Of the Phage Laboratory And Labor...mentioning

confidence: 99%

Section: Guideline No 3: Genetic Safety Checkmentioning

confidence: 99%

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Practical Assessment of an Interdisciplinary Bacteriophage Delivery Pipeline for Personalized Therapy of Gram-Negative Bacterial Infections

et al. 2022

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Pharmacokinetics and Biodistribution of Phages and their Current Applications in Antimicrobial Therapy

Kang,

Bagchi,

Chen

2023

Advanced Therapeutics

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Antimicrobial resistance remains a critical global health concern, necessitating the investigation of alternative therapeutic approaches. With the diminished efficacy of conventional small molecule drugs due to the emergence of highly resilient bacterial strains, there is growing interest in the potential for alternative therapeutic modalities. As naturally occurring viruses of bacteria, bacteriophage (or phage) are being re‐envisioned as a platform to engineer properties that can be tailored to target specific bacterial strains and employ diverse antibacterial mechanisms. However, limited understanding of key pharmacological properties of phage is a major challenge to translating its use from preclinical to clinical settings. Here, this work reviews modern advancements in phage‐based antimicrobial therapy and discusses the in vivo pharmacokinetics and biodistribution of phage, addressing critical challenges in their application that must be overcome for successful clinical implementation.

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Crossing the Chasm: How to Approach Translational Pharmacokinetic–Pharmacodynamic Modeling of Phage Dosing

Rao,

Vallé,

Mahadevan

et al. 2024

Clin Pharma and Therapeutics

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Effectively treating multidrug‐resistant bacterial infections remains challenging due to the limited drug development pipeline and a scarcity of novel agents effective against these highly resistant pathogens. Bacteriophages (phages) are a potential addition to the antimicrobial treatment arsenal. Though, phages are currently being tested in clinical trials for antibiotic‐resistant infections, phages lack a fundamental understanding of optimal dosing in humans. Rationally designed preclinical studies using in vitro and in vivo infection models, allow us to assess clinically relevant phage +/− antibiotic exposure (pharmacokinetics), the resulting treatment impact on the infecting pathogen (pharmacodynamics) and host immune response (immunodynamics). A mechanistic modeling framework allows us to integrate this knowledge gained from preclinical studies to develop predictive models. We reviewed recently published mathematical models based on in vitro and/or in vivo data that evaluate the effects of varying bacterial or phage densities, phage characteristics (burst size, adsorption rate), phage pharmacokinetics, phage–antibiotic combinations and host immune responses. In our review, we analyzed study designs and the data used to inform the development of these mechanistic models. Insights gained from model‐based simulations were reviewed as they help identify crucial phage parameters for determining effective phage dosing. These efforts contribute to bridging the gap between phage therapy research and its clinical translation.

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Considerations for the Use of Phage Therapy in Clinical Practice

Cited by 230 publications

References 192 publications

Practical Assessment of an Interdisciplinary Bacteriophage Delivery Pipeline for Personalized Therapy of Gram-Negative Bacterial Infections

Practical Assessment of an Interdisciplinary Bacteriophage Delivery Pipeline for Personalized Therapy of Gram-Negative Bacterial Infections

Pharmacokinetics and Biodistribution of Phages and their Current Applications in Antimicrobial Therapy

Crossing the Chasm: How to Approach Translational Pharmacokinetic–Pharmacodynamic Modeling of Phage Dosing

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