Comparison of Phages and Antibiotics


This page aims to describe the fundamental differences between phages and antibiotics: their advantages and disadvantages, differences in application, side effects, etc., while citing some key sources.The intention is not to oppose phages to antibiotics but to understand that:
- Bacteriophages and antibiotics can be complementary.
- In cases where antibiotics have reached a therapeutic impasse, phage therapy should be considered as a solution. - Phage therapy, in many cases, can be used as an alternative to antibiotics without side effects.
- It may be beneficial to use bacteriophages and antibiotics simultaneously, making it more difficult for bacteria to develop resistance against two different attacks.
- Phages, with their ability to penetrate biofilms, can also help antibiotics regain their effectiveness.

Comparison of Therapeutic Methodologies between Bacteriophages and Antibiotics

Phages multiply and replicate when they come into contact with bacteria. They need to be in contact with the infectious focus to act.
For each bacteria, there is at least one phage, although some phages may not be able to "treat" infections, especially for intracellular bacteria. Therefore, it is necessary to identify the bacteria, search for the most effective phage (phage susceptibility testing), and have access to the infected site. Consequently, there is a need for analysis time before administering the treatment to the patient. This therapeutic methodology, which is necessary to achieve good results, requires more time and effort compared to antibiotics. This is likely a contributing factor to the widespread use of antibiotics, which are much easier to administer. Please refer to the page "Traitement par phagothérapie" for detailed information on the specific process of such treatment (not to be compared with chemical antibiotic treatments).

Antibiotics target a broad or specific range of bacteria. The treatment can be administered almost immediately to the patient, with all patients receiving the same treatment for a given type of infection.

Side effects of phages and antibiotics

Very rare, brief and fleeting side effects can occur, such as a fever for an hour or two (as with antibiotics) and mild headaches, due to bacterial lysis.

A very positive side effect of phages is their ability to strengthen the immune system. Then, when the phages can no longer find bacteria to infect, they eliminate themselves through natural pathways. It should be noted that during inhalations, discomfort may occur. Indeed, when bacterial lysis is too significant, it causes the release of many bacterial debris. This results in symptoms of bronchitis without being bronchitis. This symptom lasts between a few hours and one to two days. That's why it is recommended to practice bacteriophage inhalations under medical supervision.

The side effects of antibiotics are numerous and well-known. Due to non-targeted destruction of too many types of bacteria, especially in the gut, and depending on the types of antibiotics, the following side effects may appear: digestive disorders, bloating, nausea, diarrhea, neurological problems, tendon issues, cardiac problems, allergic reactions, mouth or vaginal yeast infections, deafness, and more.

Bacterial resistance to phages and antibiotics

BACTERIOPHAGESBacteria can indeed become resistant to phages. However, we are never in a total therapeutic deadlock with phage therapy. In fact, there is always the possibility to "work" a phage on a given bacterium to enhance its virulence. Moreover, doctors often observe that when a bacterium mutates to become resistant to a phage, it becomes susceptible to antibiotics again.Furthermore, it is a natural process; if bacteria seek to resist phages, the phages in turn seek to enhance their virulence against the bacteria. This process has existed for billions of years (since the arrival of bacteria and phages on Earth). This explains why there are no multi-phage-resistant bacteria and it represents a natural balance that is beneficial to the planet’s ecosystem.It should be noted that, although not all have been found, it is estimated that there are at least one phage per bacterium, but rather an average of 10 to 100 different phages for a given bacterium (Source: US National Library of Medicine).Finally, the use of "cocktails" of phages (5 to 7 different phages per vial) by Georgian doctors serves to prevent the bacterium from mutating against a single phage, but instead forces it to defend against multiple phages. Thus, its mutation to become resistant becomes much more complex, and therefore difficult to achieve.

ANTIBIOTICSThe intensive use of antibiotics has led to the "selection" of bacteria that they could not destroy: the so-called multi-resistant bacteria. Indeed, only these remain, unharmed by the effect of antibiotics and can proliferate. Once a bacterium resistant to antibiotics has infected a patient, they find themselves in a "therapeutic deadlock" as there are no known treatments left to treat them. Antibiotic resistance is a global health issue. Projections estimate up to 10 million deaths per year worldwide by 2050 due to multi-resistant bacteria (source: Institut Pasteur) because we are running out of effective antibiotics (source WHO: The world is running out of antibiotics).

Targeting bacteria

Phages multiply by reproducing when they come into contact with bacteria. Thus, they need to be in contact with the infectious site to act.
When phages no longer find bacteria to infect, they eliminate themselves through natural pathways.

Antibiotics at best target a family of bacteria, but never only the pathogenic bacterium. As a result, they blindly destroy non-pathogenic bacteria that can be beneficial to our digestive and immune systems (intestinal flora).

Production and Quality

Definition of a medication (source: Cambridge Dictionnary):"a medicine, or a set of medicines or drugs, used to improve a particular condition or illness".

American definition : "any substance used to treat an illness or disease, esp. a drug"
Definition of Good Manufacturing Practices according to WHO: One of the elements of quality assurance, ensuring that products are consistently produced and controlled to meet the quality standards appropriate for their intended use and as required by the marketing authorization.

The Good Manufacturing Practices (GMP) system is not suitable for bacteriophages. Therefore, it is impossible to produce phages according to GMP. Phages are not made of chemically manufactured molecules with the same "recipe" in a factory, but rather living organisms (considered alive by some). Such production standards are not applicable to them and do not exist to date. This is an argument against their authorization.

The current standard for pharmaceutical manufacturing facilities in Georgia is the national Georgian standard. Eliava Bio Preparation laboratory fully complies with this standard. The national Georgian standard is a strict and high-quality manufacturing regulation that ensures compliance of manufacturing facilities with the declared standards. Georgia is in the process of validation to become a member of PIC/S, which is the "Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme." All of Europe, North America, the Commonwealth, and a few others are part of it.

Bacteriophage products manufactured by Eliava BioPreparations are registered pharmaceutical products in Georgia. The production process and quality control are carried out in full compliance with national standards for pharmaceutical manufacturing by the "Ministry of Labor, Health, and Social Affairs of Georgia." Quality control of each batch manufactured is conducted in an internal quality control laboratory as well as in an independent third-party laboratory to test the quality of pharmaceutical products.

The sterility control of all phage products by Eliava BioPreparations is carried out in total compliance with sterility (2.6.1) and the guidelines for the sterility test (5.9.1) in accordance with the European Pharmacopoeia. It is also in accordance with the guidelines for sterility tests (3.2) by the WHO International Pharmacopoeia.

The production of antibiotics complies with all the standards for marketing medications (Good Manufacturing Practices, Marketing Authorization, etc.).

COVID-19: Usefulness of Phages and Antibiotics

Phages can reduce the risk of death from COVID-19. In fact, phages can also induce antiviral immunity while contributing to maintaining a balanced immune response. Moreover, by inhibiting the activation of NF-κB and ROS production, phages can downregulate excessive inflammatory reactions relevant to the pathology and clinical progression of COVID-19 (Source: [insert source]). Phages in the fight against COVID-19)

Antibiotic therapy does not appear to have significant benefits in the treatment of COVID-19.(source : ). Even though studies have been conducted using azithromycin in combination with hydroxychloroquine, their results do not seem conclusive when used alone.(source : French society of pharmacology and therapeutic : source: )