Phage Therapy Pharmacology

Abedon, Stephen T.

doi:10.1016/b978-0-12-387044-5.00001-7

Cited by 100 publications

(67 citation statements)

References 28 publications

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“…Such concentrations, particularly as sustained locally over the course of treatments, typically should be adequate to achieve bacterial clearance. See Abedon [93] for defense of 10 8 phages/mL as a reasonable target for local phage densities, achieved via either active or passive means, towards successful treatment outcome, which in turn is roughly consistent with arguments and evidence supplied by the following publications [45, 50, 85, 91, 116, 117, 119, 185–190]. Note, though, that for particularly poorly adsorbing phages the achievement of phage densities that are even higher than 10 8 /mL at their site of activity may be necessary to realize adequate bacterial killing.…”

Section: Phage-bacterial Interactionssupporting

confidence: 69%

“…Fortunately, phage in situ replication can offset failures to supply sufficient phage densities through traditional dosing, ideally supporting phage population growth to relatively effective densities such as in the range of 10 8 / mL [93]. For further discussion of issues of phage adsorption during phage therapy, see Abedon [85, 92, 116, 117] as well as Abedon and Thomas-Abedon [91]. …”

Section: Phage Virion Eco-physiologymentioning

confidence: 99%

“…Alternatively, it is especially in situ phage amplification, as can occur in association with phage infection along with subsequent bacterial killing, that can counteract depletion in phage densities. Not to be overlooked, the traditional approach in pharmacology to addressing issues of drug in situ depletion is to provide additional drug, or phages [93, 117], in multiple doses over the course of treatment. See Figure 8 for summary of especially the impact of these various pharmacokinetic processes during phage therapy.…”

Section: Phage Virion Eco-physiologymentioning

confidence: 99%

“…The adsorption rate constant helps determine a phage's minimum effective concentration as an antibacterial agent as well as other measures of a phage's virion-density-dependent impact on target bacteria [117]. See, though, a recent study addressing this issue of MIC determination for bacteriophages [146] using what can be described also as an in vitro phage virulence test [41].…”

Section: Phage-bacterial Interactionsmentioning

confidence: 99%

“…If that is not the case, then simply phage-mediated bacterial killing, perhaps in combination with phage-mediated bacterial lysis, may be sufficient to achieve phage therapy success. These issues are more than academic as they go to the heart of a number of pharmacologically relevant questions in phage therapy [93, 117]. How many phages should be applied per dose?…”

Section: Phage-bacterial Interactionsmentioning

confidence: 99%

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Phage Therapy: Eco-Physiological Pharmacology

Abedon

2014

Scientifica

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Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies), impact on body-associated microbiota (as ecological communities), and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.

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Section: Phage-bacterial Interactionssupporting

confidence: 69%

Section: Phage Virion Eco-physiologymentioning

confidence: 99%

Section: Phage Virion Eco-physiologymentioning

confidence: 99%

Section: Phage-bacterial Interactionsmentioning

confidence: 99%

Section: Phage-bacterial Interactionsmentioning

confidence: 99%

See 3 more Smart Citations

Phage Therapy: Eco-Physiological Pharmacology

Abedon

2014

Scientifica

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Virus Production Under Suspension Conditions

Merten

Bakker

Vorlop

et al. 2014

Industrial Scale Suspension Culture of Living Cells

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Ameliorating the antimicrobial resistance crisis: phage therapy

Saha

Mukherjee

2019

IUBMB Life

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Propelled by the overuse and inappropriate use of antibiotics, antimicrobial resistance is now widespread in the environment, leaving us with limited drugs for treating a large number of resistant pathogens. The use of bacteriophages that kill bacteria has come up as a viable alternative to circumvent the antimicrobial resistance crisis, and phage therapy‐based approaches are fast advancing in recent times. In this minireview, we try to describe the advantages associated with phage therapy and update the latest developments in the field including the clinical trials that are underway. Particularly, we highlight the synergistic bactericidal effect of phages in the presence of sub‐lethal dose of antibiotics and the potency of lytic phages, and their hydrolytic enzymes in expunging pathogens from drug‐tolerant biofilms and animal farm produce. We also discuss how major challenges, including human immune response to phage components, development of bacterial resistance and elimination of intracellular pathogens, presented as potential setbacks to the implementation of phage therapy is being removed using engineered phages and novel formulations. © 2019 IUBMB Life, 2019

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Phage Therapy Pharmacology

Cited by 100 publications

References 28 publications

Phage Therapy: Eco-Physiological Pharmacology

Phage Therapy: Eco-Physiological Pharmacology

Virus Production Under Suspension Conditions

Ameliorating the antimicrobial resistance crisis: phage therapy

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