INTRODUCTION

Antibiotics are drugs that are used to treat bacterial infections. They have
been used for millennia to treat infections, although until the last century or
so people did not know the infections were caused by bacteria. The first
modern antibiotic, arsphenamine, was discovered in 1909 by Paul Ehrlich, a
German physician. The discovery of penicillin by Alexander Fleming in 1928
marked the beginning of the so-called “golden era” of antibiotics. During the
golden era, most of the antibiotic classes we use as medicines today were
discovered and introduced to the market. However, since the 1950s, there has
been a decline in the discovery rate of new antibiotics, and no new classes
have been discovered since then [Rustam I. Aminov et al. 2010]. Today, there
are very few novel antibiotics under development, and antibiotic-resistant
bacteria that survive antibiotic treatment are becoming more and more
common, making available antibiotics ineffective [Fair. et al. 2014].
Therefore, doctors have become much more careful in the way they prescribe
antibiotics, giving them only when they are absolutely necessary.

Definition and Mechanisms of Antibiotic

Resistance.

Antibiotic resistance occurs when bacteria and fungi develop the ability to
defeat the drugs designed to kill them. This resistance can be acquired
through various mechanisms, including limiting drug uptake, modifying drug
targets, inactivating drugs, and actively effluxing drugs [Wanda C Reygaert
et al 2018][CDC et al. 2022]. Bacteria use two major genetic strategies to
adapt to antibiotic attack: mutations in genes associated with the mechanism
of action of the compound, and acquisition of foreign DNA coding for
resistance determinants through horizontal gene transfer [Jose M. Munita et
al. 2016]. These mechanisms can lead to alterations in the antibiotic target,
decreased drug uptake, activation of efflux mechanisms to extrude the drug,
or global changes in important metabolic pathways [Jose M. Munita et al.
2016]. Understanding these mechanisms is crucial for designing strategies to
curtail the emergence and spread of resistance and develop innovative
therapeutic approaches against multidrug-resistant organisms [Jose M.
Munita et al. 2016]. The misuse and overuse of antibiotics have contributed
to the growing resistance problem, making it difficult, and sometimes
impossible, to treat resistant infections [CDC et al. 2022]. Therefore, it is
essential to use antibiotics judiciously to slow down the development of
resistance [CDC et al. 2022].

How Bacteria Develop Resistance: Mutation

and Selection.
Bacteria develop resistance to antibiotics through mutation and selection.
When bacteria are initially exposed to an antibiotic, those most susceptible to
the antibiotic will die quickly, leaving any surviving bacteria to pass on their
resistant features to succeeding generations. Bacteria can develop defense
mechanisms against antibiotics through random mutation of bacterial DNA,
generating a wide variety of genetic changes. Some bacteria have developed
biochemical “pumps” that can remove an antibiotic before it reaches its
target, while others have evolved to produce enzymes to inactivate the
antibiotic. Additionally, bacteria readily swap bits of DNA among both
related and unrelated species, allowing antibiotic-resistant genes from one
type of bacteria to be incorporated into other bacteria. This genetic plasticity
of bacteria allows them to respond to a wide array of environmental threats,
including the presence of antibiotic molecules that may jeopardize their
existence [Jose et al. 2016]. Mutational changes leading to resistance can
alter the antibiotic action through modifications of the antimicrobial target, a
decrease in drug uptake, activation of efflux mechanisms to extrude the drug,
or global changes in important metabolic pathways [Jose et al. 2016].
Horizontal gene transfer is also a major driver of bacterial evolution and
dissemination of antibiotic resistance genes [Jose et al. 2016][ Coleman et al
2014].

Impact of Antibiotic Resistance on Public

Health Systems.
Antibiotic resistance has a significant impact on public health systems
worldwide. The emergence and spread of drug-resistant pathogens pose a
threat to our ability to treat common infections, leading to higher medical
costs, prolonged hospital stays, and increased mortality [WHO et al. 2023]
[WHO et al. 2020]. The problem of antibiotic resistance is affecting people at
any stage of life and impacting the healthcare, veterinary, and agriculture
industries [CDC et al 2022]. Some of the key impacts of antibiotic resistance
on public health systems include:
1. Treatment failures: Antibiotic-resistant infections can be difficult or
impossible to treat, leading to treatment failures and increased patient
morbidity [WHO et al. 2023].
2. Increased risk of disease spread: Resistant bacteria can spread infections
more easily, increasing the risk of disease outbreaks and transmission to
others [WHO et al. 2023].
3. Threat to medical advances: Antibiotic resistance can undermine the
effectiveness of medical procedures that rely on antibiotics to prevent and
treat infections, such as organ transplantations, cancer therapy, and the
treatment of chronic diseases like diabetes, asthma, and rheumatoid arthritis
[CDC et al 2022].
4. Economic burden: The treatment of antibiotic-resistant infections can be
more expensive, and the economic burden of antibiotic resistance is estimated
to reach up to $100 trillion by 2050 [CDC et al 2022].
5. Impact on animal health and agriculture: Antibiotic resistance is not
limited to human health; it also affects animal health and agriculture, as
antibiotics are widely used in animal farming to promote growth and prevent
infections [CDC et al 2022].
To address the impact of antibiotic resistance on public health systems, it is
crucial to improve surveillance of antibiotic-resistant infections, strengthen
infection prevention and control measures, invest in research and
development of new antibiotics, vaccines, diagnostics, and other tools, and
promote the appropriate use and disposal of quality medicines [WHO et al.
2020].

Consequences of Antibiotic Resistance on

Treatment Outcomes.
Antibiotic resistance has significant consequences on treatment outcomes,
impacting both health and economic aspects. Studies have shown that
resistance frequently leads to a delay in the administration of
microbiologically effective therapy, which may be associated with adverse
outcomes, including increased mortality, morbidity, and cost for patients with
resistant versus susceptible infections [Gorge et al. 2003][WHO et al. 2020].
The emergence of antimicrobial-resistant infections that require the use of
second- and third-line treatments can harm patients by causing serious side
effects, prolonging care and recovery, and increasing healthcare costs [CDC
et al. 2022]. Antibiotic resistance can also affect patients' illness burden in
the community and may impact primary-care workload [Oliver et al. 2017].
Furthermore, the economic burden of antibiotic resistance is estimated to
reach up to $100 trillion by 2050, with longer illness duration and treatment,
often in hospitals, increasing healthcare costs and the economic burden on
families and societies[CDC et al. 2022][ WHO et al. 2020]. The impact of
antibiotic resistance is not limited to human health; it also affects the
healthcare, veterinary, and agriculture industries, posing a significant threat
to public health systems worldwide [Oliver et al. 2022]. Therefore,
addressing antibiotic resistance is crucial to mitigate its adverse effects on
treatment outcomes and the overall healthcare system.

Overuse and Misuse of Antibiotics.

The overuse and misuse of antibiotics have contributed significantly to the

global antibiotic resistance crisis. Antibiotic overuse occurs when antibiotics
are used when they are not needed, such as for viral infections, or when they
are prescribed for longer durations than necessary. Misuse also includes
incorrect prescribing practices, such as choosing the wrong antibiotic,
incorrect dosing, or not completing the full course of treatment. These
practices promote the development of resistant bacteria, making infections
harder to treat and leading to adverse outcomes.
The overprescribing of antibiotics, particularly in primary care, has been
identified as a significant issue, with respiratory tract infections being the
leading reason for prescribing antibiotics [Carl et al 2014]. The misuse and
overuse of antibiotics have been associated with an increased risk of adverse
effects, more frequent re-attendance, and increased medicalization of self-
limiting conditions [Carl et al 2014]. Additionally, the agricultural use of
antibiotics has environmental implications, as antibiotics given to livestock
can be excreted and dispersed through fertilizer, groundwater, and surface
runoff, contributing to the spread of resistance [C. Lee et al 2015].
To address the antibiotic resistance crisis, it is crucial to implement
multifaceted interventions to reduce overuse of antibiotics, enforce policies to
regulate antibiotic use, and promote the appropriate use and disposal of
quality medicines. This includes improving surveillance of antibiotic-
resistant infections, strengthening infection prevention and control measures,
and investing in research and development of new antibiotics, vaccines,
diagnostics, and other tools [Carl et al 2014][WHO et al. 2020]. Individual
actions, such as only using antibiotics when prescribed by a certified health
professional, following health worker's advice, and preventing infections
through good hygiene practices, are also essential in combating antibiotic
resistance.

Disadvantages: Impact on Healthcare, Morbidity,

and Mortality.

The negative impact of antibiotic resistance on healthcare, morbidity, and

mortality is well-documented in the search results. Infections caused by
resistant bacteria lead to up to two-fold higher rates of adverse outcomes
compared with similar infections caused by susceptible strains, resulting in
increased morbidity and mortality [N D Friedman et. al. 2016]. Antibiotic
resistance leads to longer hospital stays, higher medical costs, and increased
mortality, posing a significant threat to successful prevention and treatment
of infectious diseases [WHO et. al. 2020]. The overprescribing of antibiotics,
particularly in primary care, has been identified as a significant issue, with
respiratory tract infections being the leading reason for prescribing antibiotics
[Carl et al 2014]. Antibiotic resistance is a global public health threat, killing
at least 1.27 million people worldwide and associated with nearly 5 million
deaths in 2019 [Porooshat et al 2019]. Addressing antibiotic resistance is
crucial for mitigating the impact on healthcare, morbidity, and mortality.
Efforts to combat antibiotic resistance should focus on reducing the spread of
resistance, developing strategies to overcome this global challenge, and
improving the use of antimicrobial medicines [WHO et. al. 2020][ Porooshat
et al 2019].
Mechanisms of Action of Different Antibiotics.
The mechanisms of action of different antibiotics involve various
biochemical processes that target specific components of bacterial cells.
These mechanisms include inhibition of cell wall synthesis, inhibition of
protein synthesis, interference with nucleic acid synthesis, and disruption of
cell membrane function. The following are the main mechanisms of action of
different classes of antibiotics;
1. Inhibition of cell wall synthesis: Antibiotics such as penicillins,
cephalosporins, carbapenems, and glycopeptides inhibit the synthesis of
bacterial cell walls, leading to cell lysis and death.
2. Inhibition of protein synthesis: Antibiotics like aminoglycosides,
tetracyclines, macrolides, and chloramphenicol interfere with bacterial
protein synthesis by targeting the ribosomes, leading to the inhibition of
bacterial growth and reproduction.
3. Interference with nucleic acid synthesis: Antibiotics such as
fluoroquinolones inhibit the bacterial DNA gyrase and topoisomerase IV,
disrupting DNA replication and transcription, ultimately leading to bacterial
cell death.
4. Disruption of cell membrane function: Lipopeptide antibiotics, such as
daptomycin, disrupt the bacterial cell membrane, leading to depolarization
and cell death.
Understanding the mechanisms of action of different antibiotics is crucial for
selecting the appropriate antibiotic therapy and combating antibiotic
resistance. It allows clinicians to make informed decisions regarding the
choice of antibiotics based on the specific bacterial infection and its
susceptibility profile.