Question

In: Nursing

In the early 20th century, the French Canadian microbiologist Félix d’Hérelle used a virus called a...

In the early 20th century, the French Canadian microbiologist Félix d’Hérelle used a virus called a bacteriophage (“phage”) to successfully treat some diseases caused by bacteria, such as dysentery and cholera. Subsequent experiments with “phage therapy” yielded mixed results; however, and enthusiasm quickly waned—especially once antibiotics became available in the 1940s. The therapy is not currently approved in the United States.

Phage therapy involves obtaining a pure culture of a disease-causing bacterium and exposing samples of the culture to different phages to see which ones kill the bacterium. The successful phage is then administered to a patient. For skin infections, the phage is applied directly to the infected area. For systemic diseases, the phage may be given orally or delivered intravenously.

Imagine you are part of a hospital medical team conveyed to treat Jerry, a 71-year-old diabetic patient, who has been suffering from a persistent infection on his foot. His doctor has tried multiple topical antibiotics, but the infection continues to worsen, so the doctor admitted him to your hospital for a new intravenous antibiotic treatment. To Jerry’s relief, the infection cleared up; however, two weeks later, the infection returned—worse than ever. Jerry’s doctor explains that the bacterium causing the infection is a multidrug resistant strain and that Jerry’s foot will need to be amputated.

Jerry’s sister, a nurse, mentions that she studied bacteriophages and asks the doctor whether phage therapy is a treatment option.

As a member of Jerry’s medical team, answer these questions:

  • How would you respond to Jerry’s sister?
  • Which type of phage would be used for phage therapy: a lytic or a lysogenic phage?
  • What are the drawbacks of phage therapy? What are the advantages?

Solutions

Expert Solution

  • How would you respond to Jerry’s sister?

Answer:

The response to Jerry’s sister, a nurse who mentions that she studied bacteriophages and asks the doctor whether phage therapy is a treatment option would be that bacteriophage therapy can be tried if emergency FDA approval is granted.

The response of the medical team to Jerry's sister would be that bacteriophage therapy is in the experimental study phase in the USA and would need emergency FDA approval for the initiation of the same.

She has to be further explained that all the bacteriophage treatments are considered experimental with the human subject being labelled as biocontrol and require emergency approval by the FDA.

The few research centres which work on identifying the bacteriophages for the therapy have to be contacted and approval sought for the therapy from the FDA. As the therapy is experimental and not yet approved by FDA for use in humans, is unpredictable in terms of outcomes; the patient and his sister have to be ready to give consent for being a part of the experimental study consisting of the use of bacteriophages for treatment of the multi resistant bacteria in the patient.

The safety of bacteriophage therapy needs more research. There is an ongoing research on the best way to use bacteriophages in human beings as an alternative to drug therapy.

She has to be further explained that bacteriophage therapy can be used for Jerry   

1.subject to its approval as an experimental basis without guarantee of success and would form a part of the research study subject to approval from the USFDA.

2.subject to the mandatory consent on part of the patient and his relatives for the experiment.

3. subject to to the identification of a suitable bacteriophage against the multi resistant bacterial infection that Jerry is having.

4.subject to the acceptance of risks of the spread of infection to the blood stream and generalized septicemia in the wait period [ for purposes of research, bacteriophage identification and US FDA approval procedures] in the initiation of the bacteriophage therapy by the patient and his sister

Explanation:

Bacteriophages are viruses which kill the bacteria. Bacteriophage therapy is the use of the virus to kill the bacteria by direct surface application on the wound or oral ingestion or Intravenous Injection.

The bacteriophage therapy may be considered as nature's antibiotics and may be a good alternative treatment to the patients with multi resistant bacteria. However the bacteriophages which will kill the multi resistant bacteria have to be identified and applied to the surface of the wound of the patient which would be incorporating research for finding such bacteriophages and it would be an time -consuming experimental therapy.

The phage therapy is not yet approved for use on people.Few experimental phage use for resistant bacteria in antibiotic failure has been done in rare cases in past with emergency approval by the FDA.

Us San Diego health and US San Diego School of Medicine are the centres where the first person to receive successful bacteriophage therapy on an experimental basis recovered from severe bacterial infection.The centre for innovative phage therapy applications and therapeutics IPATH is a centre in North America for bacteriophages research and experimental therapy. Till now five patients have been treated at UC San Diego health with bacteriophages as a part of the experimental process.

Once Jerry and his sister understand the implications of the bacteriophage therapy including its experimental nature and and unpredictability of the outcomes, the time lag involved and the risk of generalized septicemia and consent to the same ;the medical team may have to contact the research centre and USFDA for the approval of the therapy

  • Which type of phage would be used for phage therapy: a lytic or a lysogenic phage?
  • answer 2

The lytic bacteriophages would be used to treat bacterial infections due to their specific ability to kill the bacteria in phage therapy

  explanation

  The lytic bacteriophages kill the host bacteria while lysogenic bacteriophages cause bacterial growth suppression.The specific ability of the lytic bacteriophages to kill the bacteria is used in treatment of multi resistant bacteria.

Their mechanism of action are explained below to explain the usage of lytic bacteriophages as against lysogenic bacteriophages in phage therapy.

Lytic bacteriophage== integration of the viral genome into the bacterial genome----- use of cell resources------ formation of new bacteriophages------ bacterial cell lysis and death---preferred in phage therapy.

Lysogenic bacteriophage===== integration of the viral genome into the bacterial genome---- recombination--- formation of new bacteriophages with integrated genome--decreased bacterial virulence and growth--(risk of resistant bacteria)---not preferred.

The lytic bacteriophages enter the host genome and direct the bacterial cell synthetic machinery towards production of viral genomes and proteins leading to a new generation of bacteriophages. Once the assembly and the packaging of the bacteriophages [new virions] is complete, the bacterium cell is lysed with the release of new bacteriophages that can infect the other bacterial cells.

The multi resistant bacteria need to be killed by the bacteriophage therapy.As the lytic bacteriophages have the effect of killing the bacteria; these are used for the bacteriophage therapy

The lysogenic bacteriophages integrate the viral genetic material into the host genome causing stoppage of the growth of the bacterium and transmission of the virus genomes into the daughter cells of the bacterium.The integration of the the bacteriophage genome into the the bacterial genome suppresses the growth of the bacteria but may not kill the bacteria entirely and cause emergence of resistant bacteria.Hence lysogenic bacteriophages are not preferred for the treatment of in bacteriophage therapy

What are the drawbacks of phage therapy? What are the advantages?

answer 3:

Bacteriophage therapy is in the experimental stages for use in human beings and involves a tedious,time consuming process of identification of the bacteriophage which will work against the bacteria with unpredictability of results.

The drawbacks of the bacteriophage therapy are listed below

1.The identification of the bacteriophage which will act against the multi resistant bacteria is a tedious process involving research and the use of bacteriophage therapy for human beings is still in experimental requiring approval processes which may take time.

2. difficulty in preparation of the bacteriophages involving tedious microbiological processes with unavailibilty of standard doses.

3.lack of standardization of the dose or the amount of the bacteriophages due to lack of extensive study in human beings.

4.difficulty in prediction of the success of therapy

4.triggering of unpredictable immune responses by the phages with possibility of immune overreaction or immune system imbalance.

5. difficulty to identify the bacteriophages which will work against the bacteria.

6. limitation of the bacteriophage therapy to act against only a particular bacterium against which it is studied causing the proliferation of the other pathogenic bacteria in the wound.

7. emergence of resistance in bacteria to the bacteriophages(lysogenic or temperate bacteriophage).

The advantages of the phage therapy:

1.The bacteriophage therapy used alone or in conjunction with antibiotics can help in recovery of the patient from multi resistant bacteria as well as other bacteria present in the wound leading to better healing and preventing amputation and chronicity in bad wounds with multi resistant bacteria.

2.The bacteriophage therapy is not toxic to the body and the environment and only slightly disturbs the normal good bacteria in the body having a high therapeutic index unlike the antibiotic therapy which can disturb the body commensals leading to many side effects.

3.The bacteriophages multiply and increase in number on the site at which they are applied even after application of few bacteriophages in a single dose there by multiplying the effect of killing the bacteria and the virions stay in hibernation till the new bacteria appear thereby causing long term effects.

4. The bacteriophages are natural antibiotics existing in nature and provide an alternative to the chemical antibiotics that are used to treat infections. They can be used effectively as an alternative to antibiotics are if susceptibility to resistant bacteria is known and can be used easily to kill the multi resistant bacteria

5.Untreated multi resistant bacteria can be deadly and cause serious complications including increased morbidity and mortality.The bacteriophage therapy provides an alternative though difficult, slow and unpredictable alternative for salvage therapy in multi resistant bacterial infections as a life saving effort .

6.The phage therapy has been used in processed foods and cleaning products to stop the growth of bacteria to prevent food poisings and infections.

Current approval by the USFDA for use of phage therapy

1.The phage therapy[ use of phage mixtures] has been approved in processed foods to stop the growth of bacteria such as Salmonella, listeria,E.coli, mycobacterium tuberculosis campylobacter and pseudomonas in order to prevent the growth of these bacteria and prevent food poisoning.

2. cleaning products are mixed with bacteriophages to destroy the bacteria on the surfaces to be used in places such as hospitals restaurants in other places.


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