Eradication of a Multidrug-Resistant, Carbapenemase-Producing Klebsiella pneumoniae Isolate Following Oral and Intra-rectal Therapy With a Custom Made, Lytic Bacteriophage Preparation

Corbellino, Mario; Kieffer, Nicolas; Kutateladze, Mzia; Balarjishvili, Nana; Leshkasheli, Lika; Askilashvili, Lia; Tsertsvadze, George; Rimoldi, Sara Giordana; Nizharadze, Deia; Hoyle, Naomi; Nadareishvili, Lia; Antinori, Spinello; Pagani, Cristina; Scorza, D.; Romanò, Ai Ling; Ardizzone, Sandro; Danelli, Piergiorgio; Gismondo, Maria Rita; Galli, Massimo; Nordmann, Patrice; Poirel, Laurent

doi:10.1093/cid/ciz782

Cited by 105 publications

(68 citation statements)

References 11 publications

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“…However, it remains to be established how much can be extrapolated from these studies to other mammalian organisms. Successful oral administration of phages for targeting bacteria in the intestinal tract (Corbellino et al, 2019) has led to the proposal that phages could be used as a vehicle for delivering the CRISPR system into intestinal microbiota to eliminate ARGs. However, this would require a collection of phages specially designed to target ARGs, the optimal concentration would need to be established, and knowledge of several barriers that occur in vivo would be required, such as inactivation of bacteriophages by gastric acid, and neutralization of phages by the spleen and the immune system (Merril et al, 2003).…”

Section: Utilization Of Crispr/cas System To Eliminate Mges Involved mentioning

confidence: 99%

Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance

et al. 2020

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Antimicrobial resistance (AMR) is a significant global threat to both public health and the environment. The emergence and expansion of AMR is sustained by the enormous diversity and mobility of antimicrobial resistance genes (ARGs). Different mechanisms of horizontal gene transfer (HGT), including conjugation, transduction, and transformation, have facilitated the accumulation and dissemination of ARGs in Gram-negative and Gram-positive bacteria. This has resulted in the development of multidrug resistance in some bacteria. The most clinically significant ARGs are usually located on different mobile genetic elements (MGEs) that can move intracellularly (between the bacterial chromosome and plasmids) or intercellularly (within the same species or between different species or genera). Resistance plasmids play a central role both in HGT and as support elements for other MGEs, in which ARGs are assembled by transposition and recombination mechanisms. Considering the crucial role of MGEs in the acquisition and transmission of ARGs, a potential strategy to control AMR is to eliminate MGEs. This review discusses current progress on the development of chemical and biological approaches for the elimination of ARG carriers.

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Section: Utilization Of Crispr/cas System To Eliminate Mges Involved mentioning

confidence: 99%

Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance

et al. 2020

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“…A personalized approach to phage therapy has been employed for decades at phage therapy centers such as those at the Eliava Institute in Tbilisi, Georgia, and in Wroclaw, Poland, and this approach is now being pursued in the US by Adaptive Phage Therapeutics, Inc. With this approach speed in culturing the pathogen responsible for the infection and properly selecting a phage or phages with lytic activity against it is a major consideration since the therapeutic is developed in direct response to pathogen isolation and screening. Host range is not a major concern with the personalized approach since the therapeutic is narrowly targeted to address a specific infection strain [28,34,35,43,44].…”

Section: Approaches For Phage Therapeutic Designmentioning

confidence: 99%

Bacteriophage Therapy: Developments and Directions

2020

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In an era of proliferating multidrug resistant bacterial infections that are exhausting the capacity of existing chemical antibiotics and in which the development of new antibiotics is significantly rarer, Western medicine must seek additional therapeutic options that can be employed to treat these infections. Among the potential antibacterial solutions are bacteriophage therapeutics, which possess very different properties from broad spectrum antibiotics that are currently the standard of care, and which can be used in combination with them and often provide synergies. In this review we summarize the state of the development of bacteriophage therapeutics and discuss potential paths to the implementation of phage therapies in contemporary medicine, focused on fixed phage cocktail therapeutics since these are likely to be the first bacteriophage products licensed for broad use in Western countries.

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“…However, phage associated immune activation resulting in the exacerbation of symptoms has also be observed (Gogokhia et al, 2019 ). Remarkably, phage therapy led to the eradication of multi-drug resistant Klebsiella pneumoniae by oral and rectal administration of one lytic phage in a human patient without any adverse effects (Corbellino et al, 2019 ). Phages can also act in synergy with innate immune cells to eliminated pathogens.…”

Section: The Merits Of Studying Bacteriophages and Future Prospectsmentioning

confidence: 99%

Shining Light on Human Gut Bacteriophages

Guerin

Hill

2020

Front. Cell. Infect. Microbiol.

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Eradication of a Multidrug-Resistant, Carbapenemase-Producing Klebsiella pneumoniae Isolate Following Oral and Intra-rectal Therapy With a Custom Made, Lytic Bacteriophage Preparation

Cited by 105 publications

References 11 publications

Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance

Targeting Plasmids to Limit Acquisition and Transmission of Antimicrobial Resistance

Bacteriophage Therapy: Developments and Directions

Shining Light on Human Gut Bacteriophages

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