Introduction to Antibiotic Resistance
1. Definition and Purpose of Antibiotics
• Definition: Antibiotics are medicines that kill or inhibit the growth of microorganisms,
specifically bacteria.
• Purpose: They are used to treat bacterial infections, protozoan infections, and for
immunomodulation. Antibiotics also prevent infections post-surgery and dental work.
2. Brief History and Significance in Medicine
• The history of antibiotics began with Salvarsan in 1910 for syphilis treatment.
• Discovery of penicillin in 1928 marked the start of the golden age of antibiotics, peaking in
the 1950s with numerous new discoveries.
• Antibiotics have transformed healthcare, extending the average lifespan by over 20 years.
3. Global Health Impact
• Antibiotics are crucial in preventing deadly diseases, enabling safe surgeries, cancer
treatments, and organ transplants by controlling infection risks.
• Overuse has led to antibiotic resistance, a significant medical challenge.
• Annual deaths from antibiotic resistance: At least 1 million since 1990.
4. Urgency of Addressing Resistance (Projected deaths by 2050)
• Projections indicate 4.95 million annual deaths specifically attributed to antibacterial
resistance by 2050 if current trends persist.
5. Contributors to Antibiotic Resistance
• In Developing Countries:
o Lack of surveillance of resistance development.
o Inadequate quality of available antibiotics.
o Clinical misuse.
o Ease of availability of antibiotics.
• In Developed Countries:
o Poor hospital-level regulation and excessive antibiotic use in food-producing
animals contribute significantly.
• Research and Development:
o Research on novel antibiotics is slowing due to a lack of economic incentives.
Understanding Antibiotic Resistance
1. Mechanisms of Resistance Development
• Mechanisms: Bacteria can develop resistance through various mechanisms, including
enzymatic degradation of antibiotics, modification of antibiotic targets, and active efflux of
antibiotics from the bacterial cell.
2. Intrinsic vs. Acquired Resistance
• Intrinsic Resistance: Naturally occurring resistance due to inherent structural or
functional characteristics of the bacteria (e.g., Gram-negative bacteria's outer
membrane).
• Acquired Resistance: Resistance gained through genetic mutations or horizontal gene
transfer, often involving plasmids or transposons.
3. Recent Gene Discoveries
• mcr-1: A gene that confers resistance to colistin, an antibiotic of last resort, primarily
associated with plasmid-mediated resistance.
• blaNDM-1: A gene encoding New Delhi metallo-beta-lactamase, responsible for
resistance to a broad range of beta-lactam antibiotics.
4. Contributors to Resistance
• Misuse and Overuse of Antibiotics: Prescribing antibiotics for viral infections, incorrect
dosing, and non-compliance with treatment regimens contribute to resistance.
• Human Factors: Inappropriate prescriptions, self-medication, and lack of awareness
about antibiotic use can exacerbate resistance.
• Environmental Factors: Contamination of water and soil with antibiotics and resistant
bacteria from healthcare and agricultural runoff.
• Agricultural Factors: Use of antibiotics in livestock for growth promotion and disease
prevention has a significant impact on resistance development.
5. Role of Biofilms in Resistance
• Biofilms: Complex communities of bacteria embedded in a protective matrix, making
them more resistant to antibiotics and the immune system.
• Challenges: Biofilm-associated infections are often chronic and difficult to treat due to
enhanced resistance.
6. Biofilm-targeted Therapies
• Therapies: Development of treatments aimed at disrupting biofilm formation or
enhancing antibiotic penetration into biofilms, including the use of enzymes,
nanoparticles, and novel antimicrobial agents.
This section provides a comprehensive overview of antibiotic resistance, its mechanisms,
contributors, and potential therapeutic approaches.
REFERENCES:
• Hutchings, M.I., Truman, A.W. and Wilkinson, B., 2019. Antibiotics: past, present and
future. Current opinion in microbiology, 51, pp.72-80.
• Chokshi, A., Sifri, Z., Cennimo, D. and Horng, H., 2019. Global contributors to antibiotic
resistance. Journal of global infectious diseases, 11(1), pp.36-42.
• Nicolaou, K.C. and Rigol, S., 2018. A brief history of antibiotics and select advances in
their synthesis. The Journal of antibiotics, 71(2), pp.153-184.
• Grenni, P., Ancona, V. and Caracciolo, A.B., 2018. Ecological effects of antibiotics on
natural ecosystems: A review. Microchemical Journal, 136, pp.25-39.
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Term origin: The term antibiotics means “against life”, in this case, against
microbes.
• Definition: Antibiotics are medicines that kill or inhibit the growth of
microorganisms.
• How they work: Antibiotics work by either killing bacteria or making it
difficult for them to grow and multiply.
• Types: Antibiotics can be classified as bactericidal, which kill bacteria, or
bacteriostatic, which prevent bacteria from growing.
• How they are taken: Antibiotics can be taken orally, topically, or
intravenously (IV).
• Uses: Antibiotics can treat bacterial infections, protozoan infections, and
immunomodulation. They can also be used to prevent infections after
surgical wounds and dental work.
the history of antibiotics began with Salvarsan in 1910, used to treat syphilis. This
was followed by the discovery of penicillin in 1928, which catalyzed a golden age of
antibiotics, peaking in the 1950s with many new discoveries. However, since then,
antibiotic development has slowed, while resistance has grown, leading to today’s
antimicrobial resistance crisis. Antibiotics have nevertheless transformed
healthcare, significantly extending the average lifespan by over 20 years.
Hutchings, M.I., Truman, A.W. and Wilkinson, B., 2019. Antibiotics: past, present and future. Current opinion in
microbiology, 51, pp.72-80.
Antibiotics are pivotal in medicine as they effectively treat bacterial infections,
preventing deadly diseases and reducing infection-related deaths. They enable safe
surgeries, cancer treatments, and organ transplants by controlling infection risks.
Additionally, antibiotics have drastically increased life expectancy, improved
recovery times, and reduced epidemic spread. However, their overuse has
contributed to antibiotic resistance, now a major medical challenge.
• Antibiotic resistance has claimed at least one million lives each year
since 1990.
• For antibacterial resistance specifically, projections indicate that by 2050,
there could be 4.95 million deaths annually attributed solely to antibacterial
resistance if no effective measures are taken.
• For antibacterial resistance specifically, projections indicate that by
2050, there could be 4.95 million deaths annually attributed solely to
antibacterial resistance if no effective measures are taken.
In developing countries, key contributors identified included: (1) Lack of
surveillance of resistance development, (2) poor quality of available antibiotics, (3)
clinical misuse, and (4) ease of availability of antibiotics. In developed countries,
poor hospital-level regulation and excessive antibiotic use in food-producing
animals play a significant role in leading to antibiotic resistance. Finally, research
on novel antibiotics is slowing down due to the lack of economic incentives for
antibiotic research.
Hutchings, M.I., Truman, A.W. and Wilkinson, B., 2019. Antibiotics: past, present, and future. Current opinion in
microbiology, 51, pp.72-80.
Chokshi, A., Sifri, Z., Cennimo, D. and Horng, H., 2019. Global contributors to antibiotic resistance. Journal of global
infectious diseases, 11(1), pp.36-42.
The first antibiotic to be discovered from nature was mycophenolic acid. Reported by the Italian
physician and microbiologist Bartolomeo Gosio in 1893. This seminal discovery remained
unnoticed (due to its publication in Italian) until mycophenolic acid was rediscovered in 1913 in
the United States.
The first decade of the twentieth century witnessed the emergence of the first man-
made antibacterial agent, arsphenamine (Salvarsan). Synthesized by chemist
Alfred Bertheim and approved in 1910 as a drug,
Hutchings, M.I., Truman, A.W. and Wilkinson, B., 2019. Antibiotics: past, present and future. Current opinion in
microbiology, 51, pp.72-80.
Chokshi, A., Sifri, Z., Cennimo, D. and Horng, H., 2019. Global contributors to antibiotic resistance. Journal of global
infectious diseases, 11(1), pp.36-42.
Nicolaou, K.C. and Rigol, S., 2018. A brief history of antibiotics and select advances in their synthesis. The Journal of
antibiotics, 71(2), pp.153-184.
Among the different pharmaceuticals present in soil and water ecosystems as
micro-contaminants, considerable attention has been paid to antibiotics, since
their increasing use and the consequent development of multi-resistant bacteria
pose serious risks to human and veterinary health. Moreover, once they have
entered the environment, antibiotics can affect natural microbial communities. The
latter play a key role in fundamental ecological processes, most importantly the
maintenance of soil and water quality. In fact, they are involved in biogeochemical
cycling and organic contaminant degradation thanks to their large reservoir of
genetic diversity and metabolic capability. When antibiotics occur in the
environment, they can hamper microbial community structure and functioning in
different ways and have both direct (short-term) and indirect (long-term) effects on
microbial communities. The short-term ones are bactericide and bacteriostatic
actions with a consequent disappearance of some microbial populations and their
ecological functioning. The indirect impact includes the development of antibiotic
resistant bacteria and in some cases bacterial strains able to degrade them by
metabolic or co-metabolic processes. Biodegradation makes it possible to
completely remove a toxic compound from the environment if it is mineralized.
Several factors can influence the significance of such direct and indirect effects,
including the antibiotic's concentration, the exposure time, the receiving
ecosystem (e.g. soil or water) and the co-occurrence of other antibiotics and/or
other contaminants.
Hutchings, M.I., Truman, A.W. and Wilkinson, B., 2019. Antibiotics: past, present and future. Current opinion in
microbiology, 51, pp.72-80.
Chokshi, A., Sifri, Z., Cennimo, D. and Horng, H., 2019. Global contributors to antibiotic resistance. Journal of global
infectious diseases, 11(1), pp.36-42.
Nicolaou, K.C. and Rigol, S., 2018. A brief history of antibiotics and select advances in their synthesis. The Journal of
antibiotics, 71(2), pp.153-184.
Grenni, P., Ancona, V. and Caracciolo, A.B., 2018. Ecological effects of antibiotics on natural ecosystems: A review.
Microchemical Journal, 136, pp.25-39.
