Antibiotic resistance in bacterial pathogens presents a substantial threat to the control of infectious diseases. Development of new classes of antibiotics has slowed in recent years due to pressures ...of cost and market profitability, and there is a strong need for new antimicrobial therapies. The therapeutic use of bacteriophages has long been considered, with numerous anecdotal reports of success. Interest in phage therapy has been renewed by recent clinical successes in case studies with personalized phage cocktails, and several clinical trials are in progress. We discuss recent progress in the therapeutic use of phages and contemplate the key factors influencing the opportunities and challenges. With strong safety profiles, the main challenges of phage therapeutics involve strain variation among clinical isolates of many pathogens, battling phage resistance, and the potential limitations of host immune responses. However, the opportunities are considerable, with the potential to enhance current antibiotic efficacy, protect newly developed antibiotics, and provide a last resort in response to complete antibiotic failure.
Increasing antimicrobial resistance rates have revitalized bacteriophage (phage) research, the natural predators of bacteria discovered over 100 years ago. In order to use phages therapeutically, ...they should (1) preferably be lytic, (2) kill the bacterial host efficiently, and (3) be fully characterized to exclude side effects. Developing therapeutic phages takes a coordinated effort of multiple stakeholders. Herein, we review the state of the art in phage therapy, covering biological mechanisms, clinical applications, remaining challenges, and future directions involving naturally occurring and genetically modified or synthetic phages.
Phage therapy has undergone a revitalization in the last 7 years, and a growing number of clinical trials are underway. This review provides a comprehensive view on the state of the art in phage therapy, covering biological mechanisms, clinical applications, remaining challenges, and future directions.
Airborne transmission of SARS-CoV-2 Prather, Kimberly A; Marr, Linsey C; Schooley, Robert T ...
Science (American Association for the Advancement of Science),
10/2020, Volume:
370, Issue:
6514
Journal Article
Abstract
Background
Due to increasing multidrug-resistant (MDR) infections, there is an interest in assessing the use of bacteriophage therapy (BT) as an antibiotic alternative. After the first ...successful case of intravenous BT to treat a systemic MDR infection at our institution in 2017, the Center for Innovative Phage Applications and Therapeutics (IPATH) was created at the University of California, San Diego, in June 2018.
Methods
We reviewed IPATH consult requests from June 1, 2018, to April 30, 2020, and reviewed the regulatory process of initiating BT on a compassionate basis in the United States. We also reviewed outcomes of the first 10 cases at our center treated with intravenous BT (from April 1, 2017, onwards).
Results
Among 785 BT requests to IPATH, BT was administered to 17 of 119 patients in whom it was recommended. One-third of requests were for Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus. Intravenous BT was safe with a successful outcome in 7/10 antibiotic-recalcitrant infections at our center (6 were before IPATH). BT may be safely self-administered by outpatients, used for infection suppression/prophylaxis, and combined successfully with antibiotics despite antibiotic resistance, and phage resistance may be overcome with new phage(s). Failure occurred in 2 cases despite in vitro phage susceptibility.
Conclusions
We demonstrate the safety and feasibility of intravenous BT for a variety of infections and discuss practical considerations that will be critical for informing future clinical trials.
Bacteriophage therapy (BT) is an emerging therapeutic strategy against multidrug resistant infections. We demonstrate safety and successful outcome in 7/10 cases treated with intravenous BT and share lessons learned, BT referral pattern, and regulatory aspects in the US.
A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic ...phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.
We highlight features associated with bacteriophage therapy that make it an attractive treatment option for multidrug-resistant infections and also discuss some of the challenges that need to be ...considered in the design and execution of clinical trials directed at evaluating the efficacy of bacteriophage therapy in humans.
The golden age of antibiotics, which lasted from the 1930s until 2005, brought a brisk clip of antibiotic discovery and fueled optimism about the victory of modern medicine over bacterial infections. ...Since then, however, with a stalled antibiotic discovery effort and wide-spread antibiotic use, antimicrobial resistance has emerged as a major global health threat. Bacteriophages, or phages (literally viruses that infect certain bacteria), have coevolved with bacteria for almost 4 billion years and are the most abundant organisms on the earth. Substantial progress is being made such that selection, engineering, and synthetic production of phages may make it possible for these lethal enemies of bacteria to be harnessed as potent allies in our battle against antimicrobial resistance.
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