





































Special Edition: Junior Clinical Research (2022), Vol. 2 No. S2 
 https://doi.org/10.47488/dhrp.v2iS2.58 

 

 

 
 

 DHR Proceedings ǀ http://dhrproceedings.org  72 2022, Vol. 2 No. S2 72-77 
   

 

COMMENTARY 

Bacteriophage Therapy: An Alternative 

Solution for Antibiotics 

 
Mandy Pina1,2, Angela Salinas1,3, Layla Arellano1,5, Srinidhi Sompalli1,4, Valeria Trevino1,3,  

Elanie Castillo1,3, Molisha Lopez1,3, April Pena1,3 
 

12nd Annual Junior Clinical Research Internship, South Texas Academy for Education & Training in Research, DHR Health 

Institute for Research & Development 
2IDEA San Juan College Preparatory, San Juan, TX 
3Grulla High School, Rio Grande City, TX 
4Lamar Academy/ McAllen Memorial High School, McAllen, TX 
5Harlingen School of Health Professions, Harlingen, TX  

 

All correspondence should be addressed to Program Director, 2nd Annual Junior Clinical Research Internship Program, DHR 

Health Institute for Research & Development, 5323 S McColl Road, Edinburg Texas, 78539 

 
Received 07/01/2022 

Accepted for publication 08/05/2022 

Published 08/05/2022 

 

Keywords: Bacteriophages; Phage therapy; virus; antibiotics, super bacteria;  

 

 

Introduction 
 

For the past 100 years, bacteriophage, or 

phage therapy, has greatly helped close the gap of 

resistance to antibiotics. This has been a great 

compliment to antibiotics and is slowly becoming an 

alternative to antibiotics. It was originally discovered 

in 1915 by Federick Twort and Felix d’Herelle in 

Great Britain, which started the beginning of 

molecular biology (1). D’Herelle coined the term 

bacteriophage meaning “bacteria eater” to describe the 

agent’s bactericidal ability (2). Phage therapy goes 

way back to the times of World War II, when armies 

from Germany and Japan would practice phage 

therapy in their medical services to soldiers, and even 

today bacteriophage therapy still persists (3). 

Bacteriophages work by killing bacteria and create a 

form of therapy that regulates itself at the sites of the 

infection and decays once the bacteria is completely 

killed (4). The use of phages has been proposed since 

its inception as a therapy to treat acute and chronic 

infections with initial successes first described in the 

disciplines of dermatology, ophthalmology, urology, 

stomatology, pediatrics, otolaryngology, and surgery 

(3). According to the United Kingdom government’s 

2016 Review on Antimicrobial Resistance, an 

estimated 700,000 people die each year globally from 

resistant infections with a projected cost of $100 

trillion and a death toll of 10 million by 2050 (5). 

Bacteriophage endolysins, enzymes that degrade the 

bacterial peptidoglycan (PG), have gained an 

increasing interest as alternative agents, due to their 

ability to kill antibiotic resistant pathogens efficiently 

when applied externally as purified proteins (6). They 

are ubiquitous in the environment and are recognized 

as the most abundant biological agent on earth. They 

are extremely diverse in size, morphology, and 

genomic organization (7). In this review, the 

information below will serve to explain the concept of 

phage therapy, from the pros and cons of phage 

therapy to the amount of availability that 

bacteriophage therapy can reach.  

 

What is a Bacteriophage? 
 

Bacteriophages, also referred to as phages or 

bacteria viruses are any type of viruses that infect 

bacteria. Like many viruses, phages are simple 



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organisms that have a core of nucleic acid surrounded 

by a protein capsid. Phages are classified in a variety 

of virus families, which include: Inoviridae, 

Microviridae, Rudivirade, and Tectiviridae (8). The 

nucleic acid that surrounds the core consists of DNA 

or RNA and can be double stranded or single stranded. 

Bacteriophage has three basic structural forms such as 

an icosahedral head with a tail, and a flamentus form 

(see Figure 1). In the process of an infection, a phage 

attaches to a bacterium and inserts its genetic material 

into the cell. Furthermore, a phage usually follows one 

of two life cycles, which is either lytic (virulent) or 

lysogenic (temperate) bacteriophage (8). The 

lysogenic cycle is when the DNA is only replicated, 

not transformed into proteins. The lytic cycle is when 

a virus hijacks a host cell, uses its components to make 

more of the virus, and then destroys and exits the cell 

and continues to infect other cells bacteriophage (8).    

 

Under certain circumstances, lysogenic 

phages can be induced to follow a lytic cycle. 

Understanding the structure of a bacteriophage allows 

us as researchers to make better decisions when it 

comes to treatment as well as understand how it reacts 

with the patient's body (9). 

 

Figure 1 

 

Why Do We Need Bacteriophages? 

 
 The need for bacteriophages, or an alternative 

medication for antibiotics, has been increasing, and 

although research on them has been going on for the 

past 100 years, the reliance on antibiotics has 

sabotaged further research on the topic (10). With the 

reintroduction, launched in early 2011 by Alexander 

Sulakvelidze, he released the new Bacteriophage 

journal where he discusses bacteriophages and how 

“they play a significant role in maintaining the 

microbial balance of the planet.” From this came a new 

spark in the research of these phages, and a resurgence 

in the practical use of these medications (3). First, we 

need these viruses to combat bacteria because of a 

process known as the antibiotic treadmill or resistance 

treadmill. This is the process of bacteria becoming 

resistant to most types of antibiotics after their usage 

because of mutations. Strains of bacteria adapt to 

become resistant towards different types of antibiotics 

resulting in increased dosages, using multiple 

antibiotics, and overall, not being able to efficiently 

treat bacterial infections. Secondly, many of these 

strains have a pattern of arising in nosocomial disease, 

a disease that is contracted from the hospital. This 

means that patients who are already being treated for 

a disease could be contracting potentially a strain of 

bacteria that is highly resistant to antibiotics which 

causes a decrease in their chances of survival. One 

example of this is with a critically ill patient with a 

multidrug- resistant bacteria Acinetobacter Baumannii 

infection, who was also combatting COVID-19 at the 

time. (11) This patient essentially had a slim to none 

chance of survival and his condition worsened even 

with the antibiotics that the bacteria strain seemed 

susceptible to. However, through bacteriophage 

therapy the patient’s condition improved greatly and 

he made a recovery (11). Therefore, because of the 

effectiveness of this treatment, there needs to be more 

access to this treatment and more rigorous clinical 

trials in order to get this therapy available for 

widespread use across Texas and The Rio Grande 

Valley. 

 

The Process of Bacteriophage Therapy 

 
As before mentioned, a large reason 

bacteriophage are needed is because of a process 

known as the resistance treadmill. Approximately 100 

years ago, antibiotics became the gold standard for 

treating bacterial infections. However, a new crisis has 

occurred where bacteria have become highly resistant 

to multiple antibiotic treatments, and not all antibiotics 

react well to everyone’s body (7). 

Because of this we need to outpace the bacteria to 

solve the antibiotic resistance crisis.  The rapid 

increase in AMRB (antimicrobial resistance bacteria) 

led researchers to look for alternative treatments, and 

currently one of the most promising ones are 

bacteriophages. Current research is being done on the 

use of phages and lytic proteins, mainly against drug 

resistant bacterial infections, and potentially as an 

alternative for antibiotic treatments (14). The reason 

bacteriophages are more efficient than antibiotics is 

because super bacteria have yet to become resistant to 

bacteriophages. There are also many more advantages 

to bacteriophages over antibiotics, such as the high 

therapeutic index and having fewer side effects, and 

their specialty and other safety for the host organism, 

including the intestinal microbiota (14). 

 



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To put it simply, bacteriophages are the 

predators for bacteria. While this seems very broad, 

that is what they do. Whether it is a urinary tract 

infection, or a strain of E. Coli, phage therapy has been 

proven to effectively treat these infections with no 

major side effects reported (12). Although there are yet 

to be more rigorous clinical trials on the treatment, 

there are many benefits to be considered. There are 

different routes of administration depending on the 

area of infection on the human body. One option is oral 

treatment that can be given three times a day. This is 

done by first neutralizing the gastric acid so the phages 

can thrive and spread, achieved by giving the patient 

sodium bicarbonate or bicarbonate mineral water 

(baking soda) (12). The second way it is administered 

is locally by applying a moist bandage with the phages 

onto an open wound to allow the phages to enter the 

body (12). It can also be administered using drops on 

the eyes, or in the mucous membrane, through 

intravenous drip, or by nebulization (12). The goal of 

all of these methods is to allow the phages to enter the 

body without being destroyed by our body's defenses, 

stomach acid, the skin, and our eyelashes/ nose hairs 

(12). By doing this the phages are allowed to safely 

enter the body and kill the strains of bacteria causing 

the infection. Once inside the body, the bacteriophages 

work through a process named lysis. The virus 

infiltrates the bacteria’s cell membrane by injecting its 

own DNA and RNA. It then creates up to 1,000 copies 

of itself and causes the bacteria to lyse or burst (1). 

Then, once the bacteria is gone it will stop multiplying 

and remain dormant until more bacteria enters the 

body. Furthermore, the phages will not attack human 

cells because they have high specificity, meaning they 

only attack the bacteria (13). The therapy lasts about 

1-16 weeks and is highly effective. 

 

Overall, the process of bacteriophage therapy 

is very simple and takes a short time period with mild 

side effects reported.  

 

Advantages on Bacteriophage Therapy 

 
 The use of bacteriophages as antimicrobial 

agents is one possible replacement option for 

antibiotics (15). Lytic Bacteriophages are able to kill 

antibiotic-resistant bacteria at the end of the phage 

infection cycle. Thus, the development of phage 

therapy is potentially a way to improve the treatment 

of bacterial infections (16). While not common in 

South Texas, but talked about for future resources, 

phage therapy is an important alternative to antibiotics 

in the current era of drug-resistant pathogens. Another 

reason this type of therapy is beneficial is because 

these phages cannot infect human cells (17). Phage 

therapy is a natural and secure form of antibiotics 

working to treat infections and to use the bacteria to 

replicate themselves which results in a cycle of killing 

bacteria while also producing more copies to keep 

destroying. Because of these bactericidal agents, 

bacteria get infected and do not regain their viability, 

meaning once it is killed it remains dead whilst other 

antibiotics are bacteriostatic, meaning they only stop 

the growth of bacteria contributing further to its 

resistance. Another advantage is the auto “dosing” 

factor of bacteriophages, it has been proven to 

reproduce in areas where the host is located making 

them even more effective in curing an infection (17). 

Some other advantages include non-toxicity, phages 

are made of proteins and nucleic acids that are 

nontoxic (something a lot of antibiotics cannot claim), 

and although they can cause harmful responses from 

the immune system, they can be prevented by using 

purified phage preparations to prevent anaphylactic 

reactions (the immune system releases a flood of 

chemicals resulting in the body going into shock) (17). 

Minimal shock to normal flora, unlike most antibiotics 

that are broad spectrum, bacteriophages do not harm 

the microbiome that is found inside of our bodies 

whilst antibiotics tend to harm or kill the “good” 

bacteria within us that maintain balance. Lack of cross 

resistance, since super bacteria only have resistance 

mechanisms made for antibiotics, the difference of the 

attack system of phages allows the phages to kill these 

types of bacteria more effectively, (think of it as a 

surprise attack). Bacteriophage may have single dose 

potential, because of their auto-dosing, there is 

potential for the phages to be applied only once and 

allow them to multiply and kill. Although culturing the 

bacteria can be expensive for testing, phage 

purification prices are declining due to improvements 

in the technology and compared to prices of 

pharmaceuticals is relatively low (17). 

 

Disadvantages of Bacteriophage Therapy 

 
Concerns about using phages as antibacterial 

agents can be distinguished into four categories: (1) 

phage selection, (2) phage host-range limitations, (3) 

the “uniqueness” of phages as pharmaceuticals, and 

(4) unfamiliarity with phages (17). When dealing with 

bacteriophage therapy, one of the most common 

disadvantages is that researchers must choose one 

specific phage and weigh whether the benefits of 

phage therapy outweigh the risks. Each bacteriophage 

is unique in its own way which could be a 

disadvantage because it is harder to have concrete 

research on each of them. The most common and also 

biggest disadvantage is the limited knowledge about 

the effectiveness of phage therapy. Having limited 



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information makes it harder to do research and have a 

positive outcome when it comes to experimenting with 

phages, and phage therapy. And even though it is 

classified as GRAS (Generally Regarded as Safe) by 

the FDA, the general public regards these phages as 

equivalent to an antigen (an organism that causes 

disease) instead of as a cure. However, so far people 

have not been resistant to this treatment because it is 

known as a “phage” rather than a virus. Some other 

disadvantages to consider, these are live organisms 

that can trigger the human immune system to respond 

and can carry endotoxins, which are normally cleared 

in the phage preparation stage. There is also a narrow 

host range, or only a small range of bacteria can be 

targeted by phages, however this can be solved by 

mixing phages (otherwise known as phage cocktails) 

and can create a broader spectrum for this therapy (17). 

 

Availability of Bacteriophage Therapy 

 
 Recent studies of bacteriophage therapy have 

been successful, which helps increase the probability 

of the therapy to become more common in all regions. 

As phage therapy is considered safe, this leads to 

possible use in the future for patients who have drug 

resistant infections. One reason why phage therapy 

hasn't been approved yet is because antibiotics 

prescribed are more available to the public and are 

considered to be safer by the FDA. Currently there is 

ongoing research on the best way to use phages and 

phage therapy on pathogens, and how to make it more 

available to the public in the near future. Since phage 

therapy has not been approved in the US or Europe, 

there have only been rare cases where it was used. Our 

hope is that more research and more trials can be done 

on this topic to make the treatment more available to 

the public. 

 

One such study was performed at DHR 

Health in 2021 (11). While not commonly heard of in 

the Rio Grande Valley, there have been a few 

exceptional cases in which bacteriophage therapy was 

used experimentally. Currently, there is not a standard 

of care regimen for phage therapy as it is still in the 

experimental phase. Some research indicates about 1-

16 weeks for the therapy, and because of auto-dosing, 

a single dose can be effective enough to treat the whole 

infection (13, 17). Phages are currently undergoing 

study and experimental use for future and safer use on 

humans.  

 

 

 

 

Target Age Groups 

 
When working with bacteriophage therapy 

target age groups are not specified. It has been 

experimented on people of all different ages who have 

the issue of not being able to intake antibiotics. Any 

person who is not able to utilize antibiotics because 

they have no function on them are considered for this 

experimental phase. They are known to be used for 

people of all ages above five to fight off multidrug 

resistant bacteria (18). 

   

Conclusion  

 
This treatment would benefit RGV patients in 

several ways. One reason is that using bacteriophage 

therapy has no major side effects. Secondly, it can be 

administered in several ways such as eye drops, in the 

mucous membrane, applied locally to an open wound, 

can be given intravenously or even through 

nebulization. Antibiotics can be replaced with the use 

of bacteriophages as antimicrobial agents. Using a 

bacteriophage is a way to end the infection cycle, and 

as mentioned earlier, it is a safer method to eliminate 

drug resistant pathogens. Bacteriophages, being a 

natural bacteria predator, have become a greatly used 

alternative or even a supplement to reduce the need for 

antibiotics because bacteria can develop resistance to 

conventional antibiotics.  

 

In general, it can be said that phage therapy, 

long overshadowed by chemical antibiotics, is 

gathering renewed interest in western medicine. This 

stems from the rise in frequency of multidrug-resistant 

bacterial infections in humans (19). According to Lin 

et al., “The available literature on the use of phages 

and phage-derived proteins for combating bacterial 

infections, specifically those of multidrug-resistant 

bacteria, increasingly shows promise for the prospect 

of phage therapy as either an alternative or a 

supplement to antibiotics'' (5). Bacteriophage therapy 

is an opportunity to help cure patients in the RGV with 

multi-drug resistant infections.  

 

Acknowledgments 

 

Dr. Monica Betancourt-Garcia, MD, Scientific 

Director; Melissa Eddie, MS, Program Manager; 

Xochitl Lopez, BS, Program Coordinator 

 

 

 



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Funding 

 

Funded by DHR Health Institute for Research & 

Development; DHR Health; Region One ESC 

GEARUP College Ready, Career Set! Region One 

ESC GEARUP College Now, Career Connected and 

Region One ESC PATHS 

 

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