Antibiotics are crucial for treating various types of infections affecting the throat, lungs, ears, digestive tract, urino-genital tract, skin, and more. In 1928, Dr. Alexander Fleming accidentally discovered the first antibiotic, Penicillin, which is produced by a fungus. This pioneering antibiotic, Penicillin, became publicly available for the first time in 1946 in the United Kingdom. Subsequently, numerous antibiotics from the 1st to the 4th generations were discovered up until the last decade.
Wide range of infections caused by bacteria
Antibiotic resistance
These antibiotics remain effective for decades to control various types infections but over the time bacteria find the way to save themselves from the attack of antibiotics. The process is called antibiotic resistance. World Health Organization (WHO) has warned it as one of the biggest threats to global health. As per Centre for Disease Control (CDC) more than 2.8 million antimicrobial-resistant infections are occurring per year in U.S only. In 2019, 4.95 million deaths worldwide were recorded due to infections caused by the resistant strains of bacterial species.
Many bacteria such as Pneumonia causing Klebsiella pneumoniae and Streptococcus pneumoniae, urinary tract infections causing E. coli, food poisoning or skin and lungs infections causing Staphylococcus aureus and many other bacteria are becoming resistant to various commonly used antibiotics.
Tuberculosis (TB) causing bacteria Mycobacterium tuberculosis is becoming resistant to many first-line TB drugs e.g., isoniazid and rifampicin. The use of second-line drugs, are expensive and toxic. In some cases, bacteria do not respond to even the most effective second-line TB drugs. The main reason for multidrug resistant TB is that person has to take antibiotics over an extended period, often lasting six months or more and Factors such as forgetfulness, wrong combination of drugs or not adhering to the recommended dosage regularly, can contribute to treatment failure and the emergence of drug-resistant TB.
To understand why antibiotics are becoming increasingly ineffective? you first need to understand the mechanism of action of antibiotics.
Following are the basic mechanisms by which antibiotics kill microbes:
1. Preventing the cell
wall synthesis: Many bacterial cells have a rigid
cell wall to protect and support the bacteria. Antibiotics such as penicillin,
vancomycin and cephalosporins inhibits the synthesis of an important enzymes transpeptidases
thus preventing the formation of the bacterial cell wall. This leads to
bacterial cell lysis and death.
2. Preventing protein
synthesis: Bacterial ribosomes make various
proteins and enzymes important for survival of the bacteria. Antibiotics such
as aminoglycosides, tetracyclines, and macrolides attack ribosomes
and prevents protein synthesis leading to bacterial cell dysfunction and death.
3. Preventing synthesis
of bacterial DNA: Antibiotics such
as fluoroquinolones attacks bacterial enzymes DNA gyrase and
topoisomerase IV require for synthesis of bacterial DNA. Without DNA
replication and repair, bacteria cannot survive or reproduce.
Antibiotics
such as Sulfonamides and Trimethoprim inhibit the synthesis of folic acid
required for nucleotide synthesis. In absence of folic acid Bacteria cannot
form basic structural unit of nucleic acids (DNA or RNA) and die.
4. Inhibiting
formation of cell membrane: Antibiotics such
as polymyxins and daptomycin prevents arrangement of lipid components in bacterial
cell membranes causing leakage of intracellular contents and ultimately lead to
bacterial death.
Why antibiotics are not working
Over the time bacteria develops different
techniques to save themselves from attack of antibiotics making them resistant
and such processes includes:
1. Many disease-causing Bacteria such
as E. coli, Pseudomonas aeruginosa,
Klebsiella pneumoniae develop ability to produce enzyme called β-lactamase. This enzyme breakdown
the β lactam drugs such as penicillin and make them ineffective
against these bacteria.
2. Penicillin-binding proteins (PBPs)
are important for formation of cell wall in bacteria. But antibiotics such as
penicillin and its derivatives methicillin, oxacillin etc. binds with PBPs and
make them ineffective. However, Certain resistant Bacteria eg., Methicillin
resistant Staphylococcus aureus (MRSA) develop the gene which can
produce penicillin-binding protein 2a (PBP2a). This modified
protein has lower binding affinity for beta-lactam antibiotics, allowing cell
wall synthesis even in the presence of these antibiotics. Hence,
bacteria survive and become resistant against penicillin
and its derivatives methicillin, oxacillin etc.
3. Bacteria changes the permeability of its cell membrane preventing
entry of antibiotics inside the cell or form efflux pumps in the cell
membrane which actively pump out the antibiotics from the bacterial cell, preventing
it from reaching effective concentrations inside the cell.
4. Bacteria protect themselves by formation
of slimy biofilms. When certain bacteria attach to a surface e.g., Mucus membrane
of human host, starts to multiply and secrete a slimy extracellular matrix composed
of polysaccharides and certain proteins that covers the microcolonies of
bacteria. Dental caries (tooth decay) are also caused by formation of
biofilm on the tooth. This biofilm provides structural support and protection to
the bacteria. Biofilm becomes a physical barrier for antibiotics preventing them
from reaching the bacteria cells deep within the biofilm which contribute to
antibiotic resistance.
5. As mentioned earlier, certain
antibiotics such as Vancomycin kills the bacteria by preventing the synthesis of
protective cell wall. But certain bacteria such as vancomycin
resistant enterococcus (VRE) changes its cell wall composition
(altering
the terminal D-alanine residues required
for
cross-linking of peptidoglycan subunits). Antibiotic
vancomycin unable to act on this altered cell wall making
this antibiotic ineffective and bacteria grows cell wall making it resistant
against such antibiotics.
6. Certain antibiotics such as aminoglycosides,
tetracyclines, and macrolides attack ribosomes and prevents protein synthesis leading
to bacterial cell dysfunction and death. But some bacteria modify specific ribosomal RNA
by mutation in genes encoding the rRNA. These modifications change the
structure of the ribosome, making it less susceptible to the attack by
antibiotics hence bacteria become resistant e.g. in Staphylococcus and beta hemolytic Streptococcus
becomes resistant to antibiotic clindamycin.
7. Bacteria may transfer such
mutated genes to other bacteria through a process called conjugation allowing the rapid spread of
resistance traits to many other bacteria.
What are we doing wrong to promote antibiotic resistance
The common most practices and behaviors that contribute to the development and spread of antibiotic resistance includes:
1.
Overuse and Misuse
of Antibiotics
Some healthcare
providers, chemists, pharmacists and even doctors prescribe antibiotics to
person suffering from viral infections such as in
common cold, flu, or most cases of bronchitis. Antibiotics cannot treat viral infections still their repeated or overuse kills weak bacteria
but some of them adapts to higher concentrations of antibiotics by undergoing mutation and hence acquire resistance. Such bacteria are called
“Super bugs”. The aimless use of antibiotics also kills helpful or good
bacteria which normally keeps the overgrowth of harmful microbes under check. But,
in absence of competition harmful resistant super bugs become the dominant
population and spreads directly or indirectly to other humans as well. Due
to their dominance and resistance, certain antibiotics remain ineffective in
controlling the infection.
Antibiotics remain ineffective against Super Bug
2. Incomplete
Treatment Courses
When an
infected person prescribed with antibiotic course for a definite period, prematurely
discontinue the antibiotic treatment can lead to the survival of infection
causing bacteria. The bacteria survived than becomes more resistant to this
particular antibiotic. This incomplete exposure allows the bacteria to adapt
and develop resistance.
3. Self-Medication
Self-medication or taking medicines without a prescription with leftover antibiotics can contribute to inappropriate use and the development of resistance in similar ways as described above.
Infection or superbugs spreads in community by
1. Inadequate Hygiene
and Sanitation: spreads infection from human
to human and dirty or contaminated surface to human.
2. Poor Infection
Control: this may spread resistant
microbes from patients in hospitals, clinics, laboratories to healthy human.
3. International
Travel: as coronavirus spread all over
the world other resistant microbes can also do so with human carrier.
4. Horizontal Gene
Transfer: This
allows the transfer of resistance genes between different bacterial strains,
even those of different species. Resistant genes can be shared within bacterial
communities, spreading resistance rapidly.
How to stop antibiotic resistance
1. Public Awareness
and Education: By Engaging healthcare professionals in conveying clear messages
about antibiotic use to patients and integrating antibiotic resistance
education into school curricula.
2. Right diagnosis of
infection causing microbes: It is crucial for effective treatment and preventing the misuse of
antibiotics.
4. Research and
development: its is required to
discover new antibiotics, alternative treatments, and innovative technologies
for preventing and treating infections.
5. Strengthen regulations: it can restrict the use of antibiotics in agriculture,
aquaculture, and veterinary medicine. Overuse and misuse of antibiotics
in these sectors can contribute to antibiotic resistance.
Era of Antibiotic Ineffectiveness
If antibiotic misuse and overuse continues for extended period, all
antibiotics will become ineffective in controlling the infection. It will pose
a significant danger to public health and global well-being. The
potential consequences and dangers associated with it will be:
1. Increased Mortality Rates: Without effective
antibiotics, Infections may become deadly specially after surgeries, organ transplant,
chemotherapy, immunosuppressive therapies and childbirth.
2. Prolonged Illness and Suffering: Common infections may become more severe and protracted, leading to prolonged illness, suffering, and reduced quality of life.
3. Increased Healthcare Costs: Treating antibiotic-resistant infections will requires more extensive and expensive medical interventions, which can lead to a significant increase in healthcare costs.
4. Global Spread of Infections: Resistant bacteria may spread globally making it challenging to control the outbreaks.
In closing, let us envision a world where the power of
antibiotics continues to safeguard our health and well-being. Yet, to realize
this vision, we must act now. Embracing responsible antibiotic practices,
fostering innovation in research, global partnerships, and raising
public awareness should be our tools for shaping a future. The journey to conquer antibiotic
resistance begins with each of us, and together, we can ensure a healthier and
resilient world.
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