67
intravenously, locally and in tampons, rinses, creams and aerosols. Fifth, and most impor-
tant, is that phages are active against bacteria that have become resistant to antibiotics.
Phage therapy is not without disadvantages (see Table 2). There are no internation-
ally 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 pharma-
cokinetics of therapeutic phage preparations is delineated.26 Additional research would
be needed to obtain the type of pharmacological and toxicological data required by FDA.
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 fail-
ure to select phages lytic for the targeted bacterial species. Another concern regarding the
therapeutic use of phages is that the development of phage resistance may hamper their
effectiveness. Because bacteria are under constant threat of infection by phages, there are
strong selective pressures to acquire resistance. The development of phage-neutralizing
antibodies is another possible disadvantage that may hamper phage effectiveness. It is
also unclear how effective phages would be in treating diseases caused by intracellular
pathogens (e.g., Salmonella species), where bacteria multiply primarily inside human cells
and are not accessible to phages. Phages are more difficult to administer than antibiot-
ics, and a physician needs special training in order to correctly prescribe and use phages.
It must also be remembered that phages are complex organisms than can transfer toxin
genes between bacteria.27
Table 2. Bacteriophages vs. Antibiotics
Advantages
• Very specific (affect only targeted bacterial species)
• Replicate at the site of infection
• Occur naturally (easy to locate)
• Safe (no reports of serious adverse effects)
• Active against antibiotic-resistant bacteria
Disadvantages
• Additional research required (lack of studies)
• Development of phage resistance and phage
• neutralizing antibodies
• Not accessible to intracellular pathogens
• Difficult to administer (special training required)
• Can transfer toxin genes between bacteria
Source: References 4, 7, 22–24.
The Future
The potential for treating infectious diseases with phages has been pursued since their
discovery, but for the reasons outlined here, phage therapy is not accepted in Western
medicine. There still remain many important questions that must be addressed before
lytic phages can be endorsed for therapeutic use. Currently, FDA would have a problem
approving mixtures of phages, and the agency has yet to publish guidelines for approv-
ing phage drugs. FDA scientists have indicated concern about phages changing during
the course of manufacture, as mutations in phage genes can have unexpected effects.
However, with the continuing threat of antibiotic resistance, it is time to reconsider
developing phage therapy to the point where it can be useful in modern clinical practice.28
There is a sufficient body of data to build on and a desperate need for an alternative treat-
ment against emerging antibiotic-resistant bacteria.
Bacteriophages: Beyond Antibiotics
intravenously, locally and in tampons, rinses, creams and aerosols. Fifth, and most impor-
tant, is that phages are active against bacteria that have become resistant to antibiotics.
Phage therapy is not without disadvantages (see Table 2). There are no internation-
ally 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 pharma-
cokinetics of therapeutic phage preparations is delineated.26 Additional research would
be needed to obtain the type of pharmacological and toxicological data required by FDA.
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 fail-
ure to select phages lytic for the targeted bacterial species. Another concern regarding the
therapeutic use of phages is that the development of phage resistance may hamper their
effectiveness. Because bacteria are under constant threat of infection by phages, there are
strong selective pressures to acquire resistance. The development of phage-neutralizing
antibodies is another possible disadvantage that may hamper phage effectiveness. It is
also unclear how effective phages would be in treating diseases caused by intracellular
pathogens (e.g., Salmonella species), where bacteria multiply primarily inside human cells
and are not accessible to phages. Phages are more difficult to administer than antibiot-
ics, and a physician needs special training in order to correctly prescribe and use phages.
It must also be remembered that phages are complex organisms than can transfer toxin
genes between bacteria.27
Table 2. Bacteriophages vs. Antibiotics
Advantages
• Very specific (affect only targeted bacterial species)
• Replicate at the site of infection
• Occur naturally (easy to locate)
• Safe (no reports of serious adverse effects)
• Active against antibiotic-resistant bacteria
Disadvantages
• Additional research required (lack of studies)
• Development of phage resistance and phage
• neutralizing antibodies
• Not accessible to intracellular pathogens
• Difficult to administer (special training required)
• Can transfer toxin genes between bacteria
Source: References 4, 7, 22–24.
The Future
The potential for treating infectious diseases with phages has been pursued since their
discovery, but for the reasons outlined here, phage therapy is not accepted in Western
medicine. There still remain many important questions that must be addressed before
lytic phages can be endorsed for therapeutic use. Currently, FDA would have a problem
approving mixtures of phages, and the agency has yet to publish guidelines for approv-
ing phage drugs. FDA scientists have indicated concern about phages changing during
the course of manufacture, as mutations in phage genes can have unexpected effects.
However, with the continuing threat of antibiotic resistance, it is time to reconsider
developing phage therapy to the point where it can be useful in modern clinical practice.28
There is a sufficient body of data to build on and a desperate need for an alternative treat-
ment against emerging antibiotic-resistant bacteria.
Bacteriophages: Beyond Antibiotics