From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 66
meningitis caused by Haemophilus influenzae, lung infections caused by Klebsiella pneu-
moniae, tuberculosis, gonorrhea, opportunistic infections of the lung caused by Proteus
organisms, purulent infections related to Pseudomonas aeruginosa colonization in burn
patients, typhoid fever and bacterial dysentery caused by Shigella species (see Table 1).17
Table 1. Historical Medical Uses for Phage Therapy
• Anthrax
• Bubonic plague
• Cholera
• Dysentery
• Enteritis
• Gas gangrene
• Gastrointestinal infections
• Gonorrhea
• Lung and upper respiratory tract infections
• Meningitis
• Purulent infections in burn patients
• Staphylococcal skin disease (e.g., boils, carbuncles, furuncles)
• Tuberculosis
• Typhoid fever
• Various bacterial infections (e.g., abscesses, mastoid infections, suppurating wounds,
vaginitis)
Source: References 4, 7.
Advantages and Disadvantages of Phage Therapy
The discovery of viruses that can infect and destroy bacteria was greeted with consider-
able 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.18 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 might have been 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.19
Phages have a number of advantages compared to antibiotics (see Table 2). 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 are available where they are most needed. Antibiotics
are metabolized and eliminated from the body and do not concentrate at the site of infec-
tion. 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.20 Evolution drives the
rapid emergence of new phages that can destroy bacteria that have become resistant, i.e.,
there should be an inexhaustible supply.21 Fourth, phages appear to be safe, as no serious
adverse effects have been described. Minor adverse effects, however, have been reported
due to the liberation of endotoxins from bacteria lysed in vivo by phages.22,23 Such effects
may also be observed when antibiotics are used.24 During the long history of phage usage
in Eastern Europe and the former Soviet Union, there have been virtually no reports of
serious complications.25 Phages have been administered orally (tablets or liquid), rectally,
meningitis caused by Haemophilus influenzae, lung infections caused by Klebsiella pneu-
moniae, tuberculosis, gonorrhea, opportunistic infections of the lung caused by Proteus
organisms, purulent infections related to Pseudomonas aeruginosa colonization in burn
patients, typhoid fever and bacterial dysentery caused by Shigella species (see Table 1).17
Table 1. Historical Medical Uses for Phage Therapy
• Anthrax
• Bubonic plague
• Cholera
• Dysentery
• Enteritis
• Gas gangrene
• Gastrointestinal infections
• Gonorrhea
• Lung and upper respiratory tract infections
• Meningitis
• Purulent infections in burn patients
• Staphylococcal skin disease (e.g., boils, carbuncles, furuncles)
• Tuberculosis
• Typhoid fever
• Various bacterial infections (e.g., abscesses, mastoid infections, suppurating wounds,
vaginitis)
Source: References 4, 7.
Advantages and Disadvantages of Phage Therapy
The discovery of viruses that can infect and destroy bacteria was greeted with consider-
able 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.18 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 might have been 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.19
Phages have a number of advantages compared to antibiotics (see Table 2). 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 are available where they are most needed. Antibiotics
are metabolized and eliminated from the body and do not concentrate at the site of infec-
tion. 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.20 Evolution drives the
rapid emergence of new phages that can destroy bacteria that have become resistant, i.e.,
there should be an inexhaustible supply.21 Fourth, phages appear to be safe, as no serious
adverse effects have been described. Minor adverse effects, however, have been reported
due to the liberation of endotoxins from bacteria lysed in vivo by phages.22,23 Such effects
may also be observed when antibiotics are used.24 During the long history of phage usage
in Eastern Europe and the former Soviet Union, there have been virtually no reports of
serious complications.25 Phages have been administered orally (tablets or liquid), rectally,