Problem 2. Bacterial debris present in the Phage preparations.
Problem 3. Attempts to remove host bacteria from therapeutic preparations.
Problem 4. Rapid clearance of Phages.
Problem 5. Lysogeny.
Problem 6. Anti-Phage antibodies.
Problem 7. Failure to establish scientific proof of efficacy.
Problem 8. The scientific style of Phage investigators in the historical era.
and from VIRUS vs. SUPERBUGS :
1-Advantage
Phages are very specific and do not harm the useful bacteria that live in and on the body.
Remarks
As a result, there are no side effects like diarrhoea or secondary infections such as those that occur in treatment with antibiotics. See disadvantage 2.
2-Advantage
Due to their specificity, phages do not cause a selection of resistances in the useful bacteria that live in and on the body.
3-Advantage
We are constantly ingesting phages. In general, they are harmless to human beings. When well-purified phages are used, few side effects have been described for all types of administration.
Remarks
Because they are harmless, phages can be used for combating harmful bacteria in fattening animals and food. See disadvantage 8.
4-Advantage
Phages are an ‘intelligent’ drug. They multiply at the site of the infection until there are no more bacteria. Then they are excreted.
Remarks
See disadvantage 5.
5-Advantage
Bacteria that have become resistant to a certain type of phage continue to be destroyed by other types.
Remarks
Bacteria that have become resistant to a certain antibiotic often become resistant to other drugs more easily.
6-Advantage
Phages are found throughout nature. This means that it is easy to find new phages when bacteria become resistant to them.
Remarks
If each newly isolated phage requires approval, this procedure could become too expensive.
7-Advantage
Evolution drives the rapid emergence of new phages that can destroy bacteria that have become resistant. This means that there should be an inexhaustible’ supply.
Remarks
The development of a new antibiotic for resistant bacteria takes several years.
8-Advantage
Some resistant bacteria that have been selected during treatment with phages are less virulent and can be fought by the immune system.
Remarks
Antibiotic-resistant bacteria are generally not less virulent.
9-Advantage
Phages are also active against bacteria that have become resistant to antibiotics.
10-Advantage
Phages can be genetically modified in order to make up for some of their disadvantages.
11-Advantage
Individual components of phages (e.g. lysins) can also be used as antibiotic substances. So far resistances have not occurred despite comprehensive testing.
1-Disadvantage
There are no internationally recognized studies that prove the efficacy of phages in humans.
Remarks
Numerous animal experiments demonstrate the efficacy against different infections. The first studies on humans are underway.
2-Disadvantage
The great specificity of phages is a disadvantage when the exact species of infecting bacteria is unknown or if there is a multiple infection.
Remarks
For good results, the efficacy of phages against the infecting bacteria should be tested prior to application in the lab. For this reason, phages are less suitable for acute cases. Mixtures consisting of several phages can fight mixed infections.
3-Disadvantage
Bacteria can also become resistant to phages.
Remarks
See advantages 5, 6, 7 and 8.
4-Disadvantage
Bacteria have a type of ‘immune system’ that destroys the hereditary material of some penetrating phages. Only suitable phages can conquer this ‘immune system’.
Remarks
The efficacy of phages needs to be tested in the lab prior to use in treatment.
5-Disadvantage
In comparison to chemical molecules, phages are relatively large. For this reason, the sites in the body that can be reached by them must be carefully clarified.
Remarks
So far there have been too few pharmacological studies that have clarified these questions. Because the phages multiply as long as bacteria are present, in some cases it only takes a few phages in an inaccessible location in the body to bring about healing. It appears that phage therapy is best suited for infected sites such as wounds, where phages can be easily applied.
6-Disadvantage
Infections whose agents are hidden in the interior of human cells may be inaccessible to phages.
Remarks
In the 1940s, experiments were carried out that demonstrated good results for typhoid fever, an infection in which the agents seek refuge in human cells, at least to some extent. Researchers are trying to ‘sneak’ in phages by using genetic engineering.
7-Disadvantage
Phages that are injected into the bloodstream are recognized by the human immune system. Some of them are quickly excreted and, after a certain period, antibodies against the phages are produced by the body. For this reason, it appears that one type of phage can only be used once for intravenous treatment.
Remarks
Not all types of phages are quickly excreted. In addition, variants can be selected that can remain in the blood for a long time. The antibodies do not occur for one or two weeks.
8-Disadvantage
In comparison to chemical molecules, phages are complex organisms that can transfer toxin genes between bacteria.
Remarks
The selection of strictly lytic phages, sequencing the hereditary material of phages and toxicity tests can minimize this type of risk.
9-Disadvantage
The shelf life of phages varies and needs to be tested and monitored.
10-Disadvantage
Phages are more difficult to administer than antibiotics. A physician needs special training in order to correctly prescribe and use phages.
