We believe that the Phagebiotics Research Foundation has an important role to play in moving the phage therapy field forward. As a nonprofit research foundation we can attract funds to stimulate the development of bacteriophages as tools to combat antibiotic resistance and can facilitate research collaborations to perform the needed studies for broad approval in a cost efficient manner.
Phage therapy provides a model different than that of antibiotics from which to approach bacterial disease. As such, it offers the potential to provide treatment options for multi-drug-resistant bacterial pathogens, a problem that is becoming broader and more acute and is resulting in escalating numbers of deaths and morbidity from previously curable infections. For example, MRSA, initially found only in hospitals, is now increasingly widespread in communities, and the same pattern of resistance is increasing for the antibiotics we have held in reserve to treat life threatening antibiotic resistant staph, such as Vancomycin. This is true not only for Staph, but also for enterococcus, E. coli, C. difficile, Shigella, S. typhii, and many other pathogens, leading to broad concern about a coming post-antibiotic era.
Unfortunately there is little prospect for reversing this ominous trend with replacement antibiotics. Pharmaceutical companies have largely stopped developing new antibiotics. They have understandably determined that the manner in which new antimicrobial agents need to be used (holding them in reserve for treatment failures) is not consistent with the corporate need to obtain a return on the research and development investment for new antibiotics, and have also been discouraged by the ability of bacteria to rapidly develop resistance to the new antibiotics they do develop. Thus, if we are to improve our ability to treat the increasing number of multi-drug resistant pathogens, we will have to develop new approaches to antibacterial therapy.
In contrast to antibiotics, which kill bacteria relatively indiscriminately, phage target specific bacteria. Thus, phage therapy offers the possibility to target antibacterial medicine specifically against the pathogenic organism, while leaving the rest of the host bacterial flora undisturbed. We are increasingly recognizing the harms that come from killing symbiotic bacteria. There is strong evidence that maintenance of a healthy resident bacterial flora is a critical factor in the prevention of colonization and infection with multidrug resistant organisms. This problem is especially prevalent in the gut, where antibiotic-induced microbial imbalances lead to such opportunistic infections as C. dificile colitis, a significant cause of morbidity and mortality. The Centers for Disease Control, the World Health Organization and infectious disease experts worldwide are strongly calling for more limited and targeted use of antibiotics, and for the development of new approaches to the treatment of infectious diseases. In addition to broad spectrum antibiotics leading to risk for specific diseases such as C. dificile colitis, there is increasing evidence that the health of the microbiome can be critical in human health, and that broad spectrum antibiotics can lead to poor health outcomes through harm to the resident symbiotic flora. There is no current prospect for the development of antibiotics which could target particular bacteria very specifically as phage therapy does, killing the pathogens but not disturbing the healthy flora. Thus phage therapy is a promising approach to developing a new era of medical advances in controlling infectious disease while not harming the internal ecosystem upon which we all depend for health.
Additionally, there are infections where antibiotics are not very effective, often due to poor delivery of the antibiotic to the infection due to poor circulation or to biofilms. Phage have the ability to achieve sufficient concentration in infected tissues with poor circulation by amplifying in situ while many phage have the ability to penetrate and multiply in biofilms. An example of this effect has been described in the treatment of diabetic foot infections, especially those complicated with bone infections, which often result in amputation of the limb.
Using the natural predator-prey relationship between phage and bacteria to treat infectious disease offers many potential advantages over traditional antibiotics. However, the modern clinical studies required to properly demonstrate the efficacy, safety, and relative advantages of phage treatment are just starting to be performed in the context of western medicine, due mainly to the complications of establishing appropriate guidelines and the enormous expenses and potential financial risks of performing the initial needed clinical trials. Also, case-study clinical data is needed to help determine the best protocols for such formal trials. Various companies are attempting to test proprietary phage products, most notably a multicenter clinical trial of phage in the treatment of burn wounds in France, Belgium and Switzerland and a study of the treatment of complicated military wounds in conjunction with the Walter Reed National Military Hospital in Washington DC. Both of these studies are being done with extensive governmental support but using proprietary cocktails. Collaborative studies of phage targeting cystic fibrosis lung infections are also under way on several fronts.