Good Manufacturing Practice (GMP) Compliance for Phage Therapy Medicinal Products

Bretaudeau, Laurent; Tremblais, Karine; Aubrit, F; Meichenin, Marc; Arnaud, Isabelle

doi:10.3389/fmicb.2020.01161

Cited by 51 publications

(39 citation statements)

References 25 publications

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“…Consistent with this idea, we recovered phage-resistant bacteria from mice in all phage-treated groups, with a trend toward lower recovery in combination phage-treated mice. However, there are confounding factors (e.g., accelerated rate of decay in phage titer for certain premixed phage cocktails) that make it challenging to predict whether a particular phage cocktail will confer a net therapeutic advantage (30). Further investigation is needed in order to assess the impact of individual phages in a given phage cocktail.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophage Treatment Rescues Mice Infected with Multidrug-Resistant Klebsiella pneumoniae ST258

Hesse

Małachowa

Porter

et al. 2021

mBio

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Severe infections caused by multidrug-resistant Klebsiella pneumoniae sequence type 258 (ST258) highlight the need for new therapeutics with activity against this pathogen. Bacteriophage (phage) therapy is an alternative treatment approach for multidrug-resistant bacterial infections that has shown efficacy in experimental animal models and promise in clinical case reports. In this study, we assessed microbiologic, histopathologic, and survival outcomes following systemic administration of phage in ST258-infected mice. We found that prompt treatment with two phages, either individually or in combination, rescued mice with K. pneumoniae ST258 bacteremia. Among the three treatment groups, mice that received combination phage therapy demonstrated the greatest increase in survival and the lowest frequency of phage resistance among bacteria recovered from mouse blood and tissue. Our findings support the utility of phage therapy as an approach for refractory ST258 infections and underscore the potential of this treatment modality to be enhanced through strategic phage selection. IMPORTANCE Infections caused by multidrug-resistant K. pneumoniae pose a serious threat to at-risk patients and present a therapeutic challenge for clinicians. Bacteriophage (phage) therapy is an alternative treatment approach that has been associated with positive clinical outcomes when administered experimentally to patients with refractory bacterial infections. Inasmuch as these experimental treatments are prepared for individual patients and authorized for compassionate use only, they lack the rigor of a clinical trial and therefore cannot provide proof of efficacy. Here, we demonstrate that administration of viable phage provides effective treatment for multidrug-resistant K. pneumoniae (sequence type 258 [ST258]) bacteremia in a murine infection model. Moreover, we compare outcomes among three distinct phage treatment groups and identify potential correlates of therapeutic phage efficacy. These findings constitute an important first step toward optimizing and assessing phage therapy’s potential for the treatment of severe ST258 infection in humans.

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Section: Discussionmentioning

confidence: 99%

Bacteriophage Treatment Rescues Mice Infected with Multidrug-Resistant Klebsiella pneumoniae ST258

Hesse

Małachowa

Porter

et al. 2021

mBio

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“…The phage formulations available in the banks for clinical use should be produced in line with Good Manufacturing Practices. Several publications have outlined the key aspects of Good Manufacturing Practice for phage production 18 and quality control 19 and have suggested phage purification protocols. 20 These purification protocols include testing the final preparations to confirm the identity of the bacteriophage, viability, potency, and purity (ie, the absence of bacterial or chemical residues).…”

Section: Phage Banksmentioning

confidence: 99%

Clinical Phage Microbiology: a suggested framework and recommendations for the in-vitro matching steps of phage therapy

et al. 2021

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Phage therapy is a promising solution for bacterial infections that are not eradicated by conventional antibiotics. A crucial element of this approach is appropriate matching of bacteriophages and antibiotics to the bacterial target according to the clinical setting. However, there is currently little consistency in the protocols used for the laboratory evaluation of bacteriophages intended for antibacterial treatment. In this Personal View, we suggest a framework aimed to match appropriate bacteriophage-based treatments in clinical microbiology laboratories. This framework, which we have termed Clinical Phage Microbiology, is based on the current research on phage treatments. In addition, we discuss special cases that might require additional relevant evaluation, including bacteriophage interactions with the host immune response, biofilm-associated infections, and polymicrobial infections. The Clinical Phage Microbiology pipeline could serve as the basis for future standardisation of laboratory protocols for personalised phage therapy.

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“…Here comes the one of the sophisticated parts: absence of a well-defined body of the legislations and regulations essential to organize the use of phage products (either ready-made or not) and their position in the market ( Bretaudeau et al., 2020 ).…”

Section: Assets and Shortcomingsmentioning

confidence: 99%

“…This takes us to the astonishing world of genetically-engineered bacteriophages. It should be emphasized that genetic engineering of phages is conjured up not only to go about bacterial resistance but also as a way for vaccination, editing microbiome and drug delivery ( Bretaudeau et al., 2020 ). Here, we will highlight some of the most recent phage genomic annotation tools and the primary difficulties faced during repeated attempts of phage therapy and how genetic engineering could tackle them.…”

Section: Genetic Engineering Of Phagesmentioning

confidence: 99%

“…This is one of the first full-blown Investigational New Drug (INDs) approved for phages by the FDA, and the first ever for targeting adhesive invasive E. coli (AIEC). This paves the way for more-to-come clinical trials ( Intralytix, Inc ), therefore, a scrupulous compilation of regulatory rules has to be firmly established to allow the introduction of phages into clinical practice ( Plaut and Stibitz, 2019 ; Bretaudeau et al., 2020 ).…”

Section: Marked Real Life Experiences Involving Bacteriophagesmentioning

confidence: 99%

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Rekindling of a Masterful Precedent; Bacteriophage: Reappraisal and Future Pursuits

Abd-Allah

El-Housseiny

Yahia

et al. 2021

Front. Cell. Infect. Microbiol.

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Antibiotic resistance is exuberantly becoming a deleterious health problem world-wide. Seeking innovative approaches is necessary in order to circumvent such a hazard. An unconventional fill-in to antibiotics is bacteriophage. Bacteriophages are viruses capable of pervading bacterial cells and disrupting their natural activity, ultimately resulting in their defeat. In this article, we will run-through the historical record of bacteriophage and its correlation with bacteria. We will also delineate the potential of bacteriophage as a therapeutic antibacterial agent, its supremacy over antibiotics in multiple aspects and the challenges that could arise on the way to its utilization in reality. Pharmacodynamics, pharmacokinetics and genetic engineering of bacteriophages and its proteins will be briefly discussed as well. In addition, we will highlight some of the in-use applications of bacteriophages, and set an outlook for their future ones. We will also overview some of the miscellaneous abilities of these tiny viruses in several fields other than the clinical one. This is an attempt to encourage tackling a long-forgotten hive. Perhaps, one day, the smallest of the creatures would be of the greatest help.

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Good Manufacturing Practice (GMP) Compliance for Phage Therapy Medicinal Products

Cited by 51 publications

References 25 publications

Bacteriophage Treatment Rescues Mice Infected with Multidrug-Resistant Klebsiella pneumoniae ST258

Bacteriophage Treatment Rescues Mice Infected with Multidrug-Resistant Klebsiella pneumoniae ST258

Clinical Phage Microbiology: a suggested framework and recommendations for the in-vitro matching steps of phage therapy

Rekindling of a Masterful Precedent; Bacteriophage: Reappraisal and Future Pursuits

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