The advantages and disadvantages of phage therapy

Advantage
Remarks
  1 Phages are very specific and do not harm the useful bacteria that live in and on the body. As a result, there are no side effects like diarrhoea or secondary infections such as those that occur in treatment with antibiotics.
  2 Due to their specificity, phages do not cause a selection of resistances in the useful bacteria that live in and on the body. See disadvantage 2.
  3 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. Because they are harmless, phages can be used for combating harmful bacteria in fattening animals and food. See disadvantage 8.
  4 Phages are an ‘intelligent’ drug. They multiply at the site of the infection until there are no more bacteria. Then they are excreted. See disadvantage 5.
  5 Bacteria that have become resistant to a certain type of phage continue to be destroyed by other types. Bacteria that have become resistant to a certain antibiotic often become resistant to other drugs more easily.
  6 Phages are found throughout nature. This means that it is easy to find new phages when bacteria become resistant to them. If each newly isolated phage requires approval, this procedure could become too expensive.
  7 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. The development of a new antibiotic for resistant bacteria takes several years.
  8 Some resistant bacteria that have been selected during treatment with phages are less virulent and can be fought by the immune system. Antibiotic-resistant bacteria are generally not less virulent.
  9 Phages are also active against bacteria that have become resistant to antibiotics.
10 Phages can be genetically modified in order to make up for some of their disadvantages.
11 Individual components of phages (e.g. lysins) can also be used as antibiotic substances. So far resistances have not occurred despite comprehensive testing.
Disadvantage
Remarks
  1 There are only few internationally recognized studies that prove the efficacy of phages in humans. Numerous animal experiments demonstrate the efficacy against different infections. Additional studies on humans are underway.
  2 The great specificity of phages is a disadvantage when the exact species of infecting bacteria is unknown or if there is a multiple infection. 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 Bacteria can also become resistant to phages. See advantages 5, 6, 7 and 8.
  4 Bacteria have a type of ‘immune system’ that destroys the hereditary material of some penetrating phages. Only suitable phages can conquer this ‘immune system’. The efficacy of phages needs to be tested in the lab prior to use in treatment.
  5 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. 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 Infections whose agents are hidden in the interior of human cells may be inaccessible to phages. 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 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. 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 In comparison to chemical molecules, phages are complex organisms that can transfer toxin genes between bacteria. The selection of strictly lytic phages, sequencing the hereditary material of phages and toxicity tests can minimize this type of risk.
  9 The shelf life of phages varies and needs to be tested and monitored.
10 Phages are more difficult to administer than antibiotics. A physician needs special training in order to correctly prescribe and use phages.