Bacteriophage Therapy — Hopefully Getting Closer?

March 5, 2023 at 8:10 p.m.


Long before there were antibiotics, researchers envisioned using viruses to seek out and destroy bacteria.  

Now, as organisms continue to develop resistance to existing antibiotics, these viruses, called bacteriophages, are finding new advocates. (The name bacteriophages is derived from the ancient Greek "phagein" to devour.)  Their discovery was thought to be one of the great medical findings of the past century. However, interest has waned at least until the beginning of the COVID-19 pandemic. Hospitalized patients began contracting bacterial infections that became so drug-resistant that physicians had nothing to treat them with.  

According to a report from one physician, “We were using anything and everything that was available in our toolbox, but we were losing the battle.”

Now once again bacteriophages have recaptured researcher’s interest.  Last year, the CDC reported that superbugs flourished during the pandemic. The reasons are a perfect storm of factors: overuse of antibiotics, lapses in infection prevention including proper hand hygiene and quarantining contagious patients and sicker patients.

Definition

 According to the Food and Drug Administration (FDA), bacteriophages (phages) are defined as RNA or DNA viruses that infect bacteria without infecting mammalian or plant cells. Phages are present throughout the environment, and humans are routinely exposed to them at high levels through food and water without adverse effects.  

Phages have once again become the focus of research in the battle against antibiotic resistance in the United States. Although not currently permitted here, phages are used in other countries as antibiotic therapy.  Depending on the results of the clinical research, phages may eventually become the treatment of choice for cases where antibiotics fail, but there are a host of problems to be solved before that happens.  

In February last year, the FDA announced the first U.S. clinical trial of an intravenously administered bacteriophage therapy had been approved. The proposed phase 1 and 2 trial will evaluate the safety, tolerability and efficacy of an experimental treatment for patients with ventricular assist devices who have developed Staphylococcus aureus infections.  There had been a high unmet need in such patients which are typically very difficult to eradicate with conventional antibiotics.

Advantages And Disadvantages Of Phage Therapy  

The discovery of viruses that can infect and destroy bacteria was greeted with considerable optimism in the early 1900s. Despite the efforts of a number of investigators, their use was generally abandoned soon after the introduction of antibiotics in the 1940s.  

Lytic phages, of course, are similar to antibiotics in that they have remarkable antibacterial activity and their theoretical advantages are good reasons for renewed interest. Earlier reported results using phages may have been even better if it had been recognized that there are many types of phages and that each is specific for a special host range of bacteria. This misconception resulted in applications of phage growing on one bacterial host but with little, if any, ability to influence clinical infections caused by other bacterial strains.

Phages have a number of advantages compared to antibiotics. For one, phages are very specific, they usually affect only the targeted bacterial species.  Antibiotics target both pathogenic microorganisms and normal microflora. This affects the microbial balance in the patient which may lead to a serious secondary infection.  

Second, phages replicate at the site of infection and available where they are most needed. Antibiotics are metabolized, and eliminated from the body, and do not concentrate at the site of infection.

Third, phages are found throughout nature and it is easy to find new phages when bacteria become resistant to them.  This means that selecting new phages is a relatively rapid process that can be accomplished in days or weeks, whereas developing a new antibiotic is a time consuming process that can take several years.  Phages appear to be safe as no serious side effects have been described.  

Phage therapy is not without disadvantages.  There are no internationally recognized studies that attest to the efficacy of phages in human patients.  There are a number of publications on phage therapy, but very few papers in which the pharmacokinetics of therapeutic phage preparations is described.  

Additional research would be needed to obtain the type of pharmacological and toxicological data required by the Food and Drug Administration.   There is a paucity of appropriately conducted, placebo-controlled studies. Because of the high specificity of phages, many negative results may have been obtained because of failure to select phages for the targeted bacterial species.

Another concern regarding the therapeutic use of phages is that the development of resistance may hamper their effectiveness.  Because bacteria are under constant threat of infection by phages, there are strong selective pressures to acquire resistance.

The Future

The potential for treating infectious diseases with phages has been pursued since their discovery, but for the reasons outlined above, phage therapy is not yet accepted in Western medicine. There still remain many important questions to address before phages can be endorsed for therapeutic use. Recently, however, 66 members of Congress have put their support behind the PASTEUR Act. The bill would provide $11 billion in funding for critical need antimicrobial drugs, which would include phage therapies.

Max Sherman is a medical writer and pharmacist retired from the medical device industry.  His new book “Science Snippets” is available from Amazon and other book sellers. It contains a number of previously published columns.  He can be reached by email at  [email protected]

Long before there were antibiotics, researchers envisioned using viruses to seek out and destroy bacteria.  

Now, as organisms continue to develop resistance to existing antibiotics, these viruses, called bacteriophages, are finding new advocates. (The name bacteriophages is derived from the ancient Greek "phagein" to devour.)  Their discovery was thought to be one of the great medical findings of the past century. However, interest has waned at least until the beginning of the COVID-19 pandemic. Hospitalized patients began contracting bacterial infections that became so drug-resistant that physicians had nothing to treat them with.  

According to a report from one physician, “We were using anything and everything that was available in our toolbox, but we were losing the battle.”

Now once again bacteriophages have recaptured researcher’s interest.  Last year, the CDC reported that superbugs flourished during the pandemic. The reasons are a perfect storm of factors: overuse of antibiotics, lapses in infection prevention including proper hand hygiene and quarantining contagious patients and sicker patients.

Definition

 According to the Food and Drug Administration (FDA), bacteriophages (phages) are defined as RNA or DNA viruses that infect bacteria without infecting mammalian or plant cells. Phages are present throughout the environment, and humans are routinely exposed to them at high levels through food and water without adverse effects.  

Phages have once again become the focus of research in the battle against antibiotic resistance in the United States. Although not currently permitted here, phages are used in other countries as antibiotic therapy.  Depending on the results of the clinical research, phages may eventually become the treatment of choice for cases where antibiotics fail, but there are a host of problems to be solved before that happens.  

In February last year, the FDA announced the first U.S. clinical trial of an intravenously administered bacteriophage therapy had been approved. The proposed phase 1 and 2 trial will evaluate the safety, tolerability and efficacy of an experimental treatment for patients with ventricular assist devices who have developed Staphylococcus aureus infections.  There had been a high unmet need in such patients which are typically very difficult to eradicate with conventional antibiotics.

Advantages And Disadvantages Of Phage Therapy  

The discovery of viruses that can infect and destroy bacteria was greeted with considerable optimism in the early 1900s. Despite the efforts of a number of investigators, their use was generally abandoned soon after the introduction of antibiotics in the 1940s.  

Lytic phages, of course, are similar to antibiotics in that they have remarkable antibacterial activity and their theoretical advantages are good reasons for renewed interest. Earlier reported results using phages may have been even better if it had been recognized that there are many types of phages and that each is specific for a special host range of bacteria. This misconception resulted in applications of phage growing on one bacterial host but with little, if any, ability to influence clinical infections caused by other bacterial strains.

Phages have a number of advantages compared to antibiotics. For one, phages are very specific, they usually affect only the targeted bacterial species.  Antibiotics target both pathogenic microorganisms and normal microflora. This affects the microbial balance in the patient which may lead to a serious secondary infection.  

Second, phages replicate at the site of infection and available where they are most needed. Antibiotics are metabolized, and eliminated from the body, and do not concentrate at the site of infection.

Third, phages are found throughout nature and it is easy to find new phages when bacteria become resistant to them.  This means that selecting new phages is a relatively rapid process that can be accomplished in days or weeks, whereas developing a new antibiotic is a time consuming process that can take several years.  Phages appear to be safe as no serious side effects have been described.  

Phage therapy is not without disadvantages.  There are no internationally recognized studies that attest to the efficacy of phages in human patients.  There are a number of publications on phage therapy, but very few papers in which the pharmacokinetics of therapeutic phage preparations is described.  

Additional research would be needed to obtain the type of pharmacological and toxicological data required by the Food and Drug Administration.   There is a paucity of appropriately conducted, placebo-controlled studies. Because of the high specificity of phages, many negative results may have been obtained because of failure to select phages for the targeted bacterial species.

Another concern regarding the therapeutic use of phages is that the development of resistance may hamper their effectiveness.  Because bacteria are under constant threat of infection by phages, there are strong selective pressures to acquire resistance.

The Future

The potential for treating infectious diseases with phages has been pursued since their discovery, but for the reasons outlined above, phage therapy is not yet accepted in Western medicine. There still remain many important questions to address before phages can be endorsed for therapeutic use. Recently, however, 66 members of Congress have put their support behind the PASTEUR Act. The bill would provide $11 billion in funding for critical need antimicrobial drugs, which would include phage therapies.

Max Sherman is a medical writer and pharmacist retired from the medical device industry.  His new book “Science Snippets” is available from Amazon and other book sellers. It contains a number of previously published columns.  He can be reached by email at  [email protected]

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