Antibiotics and similar drugs, together called antimicrobial agents, have been used for the last many years to treat patients who have infectious diseases. The treatment of bacterial infections is increasingly complicated because microorganisms can develop resistance to antimicrobial agents, since the first usage of antimicrobials, the resistance among bacteria has progressively increased and has accelerated within the last 10 years. This is largely due to the increasing presence of pathogenic microorganisms with resistance to previous antibiotic agents, resulting in the administration of improper treatment, not only in humans but also in companion and food animals and the environment which has caused the rise in antibiotic resistance. Although efforts are being made in all the areas, there is an urgent need to increase the effectiveness of these interventions or some bacterial infections will become difficult if not impossible to treat reliably.

1. International Journal of Research In Science & Engineering e-ISSN: 2394-8299
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ANTIBIOTIC RESISTANCE: A RISING THREAT
Sagar Aryal1 , Mona Poudel2 , Sunil Pandey3
1Student Researcher, Department of Microbiology, St. Xavier College, Bagmati, Kathmandu,
Nepal,Broneps1@gmail.com
2Student Researcher, Department of Medicine, Nobel College of Medical Science,
Koshi, Biratnagar, Nepal, poudelmona347@gmail.com
3Elsevier Student Ambassador, Department of Medical Microbiology, Nobel College, Bagmati,
Kathmandu, Nepal, sunilpandey@nobelcollege.edu.np
__________________________________________________________________
ABSTRACT
Antibiotics and similar drugs, together called antimicrobial agents, have been used for the last many years to
treat patients who have infectious diseases. The treatment of bacterial infections is increasingly complicated
because microorganisms can develop resistance to antimicrobial agents, since the first usage of antimicrobials,
the resistance among bacteria has progressively increased and has accelerated within the last 10 years. This is
largely due to the increasing presence of pathogenic microorganisms with resistance to previous antibiotic
agents, resulting in the administration of improper treatment, not only in humans but also in companion and
food animals and the environment which has caused the rise in antibiotic resistance. Although efforts are being
made in all the areas, there is an urgent need to increase the effectiveness of these interventions or some bacterial
infections will become difficult if not impossible to treat reliably.
Keywords: Antibiotic resistance, Problem, Challenges, strategy.
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1. INTRODUCTION
Antimicrobial resistance (AMR) is resistance of a microorganism to an antimicrobial drug that was originally
effective for treatment of infections caused by it, It is one of the major public health problems especially in
developing countries where relatively easy availability and higher consumption of medicines have led to
disproportionately higher incidence of inappropriate use of antibiotics and greater levels of resistance compared to
developed countries[1]. It was soon evident that bacterial pathogens were unlikely to surrender unconditionally,
because some pathogens rapidly became resistant to many of the first effective drugs. For example, the development
of resistance to penicillin in Staphylococcus aureus by the production of a β-lactamase quickly decreased the
usefulness of penicillin for serious staphylococcal infections, especially among hospitalized patients, in whom
resistant strains are frequently found before they spread to the community [2, 24]. World Health Organization has
proposed regional strategy on antimicrobial resistance with the goal to minimize the morbidity and mortality due to
antimicrobial resistant infection to preserve the effectiveness of antimicrobial agents in the treatment and prevention
of microbial infections [24]. Initially the problem of bacterial resistance to antimicrobial drugs was solved by the
discovery of new classes of drugs, such as the aminoglycosides, macrolides, and glycopeptides, as well as by the
chemical modification of previously existing drugs. Unfortunately, there is no assurance that the development of
new antimicrobial drugs can keep pace with the ability of bacterial pathogens to develop resistance [1].
Although many International agencies like World Health Assembly, World Health Organization, European
Centre for Disease Control and resolutions highlighted the antimicrobial resistance as a major public health issue, it
will be a big challenge to tackle the problem for the policy makers and health care providers[4] .The widespread use
of antimicrobial drugs for immunocompromised patients and in the intensive care units of modern hospitals clearly
results in the selection of the multidrug-resistant organisms that cause serious nosocomial infections [5,6]. We now
find ourselves following two seemingly opposite trends. The prevalence of antimicrobial-resistant human pathogens
is rapidly increasing, but the discovery and development of new antimicrobial drugs that are active against
multidrug-resistant organisms have slowed dramatically [6]. Increasing resistance of bacteria to antibiotics has been

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documented worldwide, From the surveillance data of the Alexander project, Baquero [6] has reported rates of
penicillin resistance in 10% to 40% of strains of pneumococci in western Europe, 5% to 70% of strains in eastern
Europe, 20% of strains in South Africa, 5% to 25% of strains in South America, and 5% to 60% of strains in Asia.
In the public health point of view, it is important to look for the existing situational analysis so that appropriate
prevention can be initiated at community level to fight the problem. With this background, the study analyzed the
situation of problem burden and various factors with recent developments, challenges and strategies required to fight
the Antimicrobial Resistance. In the 60 years since their introduction, millions of metric tons of antibiotics have
been produced and employed for a wide variety of purposes, alteration in production have provided increasingly less
expensive compounds that encourage nonprescription and off-label uses[27].
1.1 Methods
In this review the data were collected by Google search engine, CDC, Medline, WHO, ASMand others.
The key words used for the search included: Antimicrobial resistance, problem burden, challenges, strategies and the
information was presented in the form of description.
1.2. Mechanism of antibiotic resistance
There are several genetic mechanisms by which resistance to antibiotics develop in bacteria, these
mechanisms give rise to resistance because they result in biochemical modifications that alter certain bacterial cell
properties that normally render the cell sensitive [16, 23]. Like as biochemical modifications that lead to resistance
include the production of enzymes that inactivate the drug; the alteration of the enzyme, protein, or receptor targeted
by the drug; the activation of drug efflux pumps that deliberately remove the drug from the cell; and the alteration of
cell-wall proteins that inhibit drug uptake [27]. There are two important types of genetic mechanisms that can give
rise to antibiotic resistance: mutation and acquisition of new genetic material [11]. In the case of mutation, the rate at
which resistance develops can be attributed to the rate at which bacteria mutate.
Figure1:Different way of antibiotic resistant to bacteria (levy, et al)

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2. INTRINSIC RESISTANCE
Intrinsic resistance is the innate ability of a bacterial species to resist activity of a particular antimicrobial agent
through its inherent structural or functional characteristics that allow tolerance of a particular drug or antimicrobial
class. This can also be called “insensitivity” since it occurs in organisms that have never been susceptible to that
particular drug [6, 9]. It is a naturally occurring phenomenon that predates antibiotic chemotherapy and is present in
all bacterial species, addition to the intrinsic resistance mediated by the bacterial outer membrane and active efflux,
can also show that a surprising number of additional genes and genetic loci also contribute to this phenotype [8].
2.1 Problem burden
Antimicrobial resistance is a major public health problem in South East Asian countries [6]. Antibiotic
resistance genes were present at very low levels prior to the introduction of antibiotics and it is largely the selective
pressure of antibiotic use and the resulting vulnerable of bacteria[28] not only in humans but also in companion and
food animals and the environment, which has caused the rise. Another major issue is that there is no national data
based on antimicrobial resistance in different pathogens except for those where there is a specific national health
program. There are some hospital based data which showed that antibiotic resistance is increasing and will be a
greater problem if not tackled properly according to present needs as in other developed countries [9]. It is the use
of antimicrobial drugs for prophylactic or therapeutic purposes in humans or for veterinary or agricultural purposes
that provides the selective pressure favoring the overgrowth of resistant organisms[2,10] In a number of countries,
many antimicrobial drugs are freely available without prescription, it varies in different places and region, therefore
local resistance patterns have to be known for appropriate antimicrobial use [11].According to WHO report’s results
the show high levels of E. coli resistance to third generation cephalosporin’s and fluoroquinolones[27,28].
Resistance to third generation cephalosporin’s in K. pneumoniae is also high and widespread. In some parts of the
Region, more than one quarter of Staphylococcus aureus infections are reported to be methicillin-resistant (MRSA),
meaning that treatment with standard antibiotics does not work [26]
2.2 Challenges
A critical issue at the regional level is the need for and difficulty in taking effective measures as the
responsibility for health remains essentially a national problem [12].Despite an early surge in cases in the 1960s,
MRSA rates generally fell in challenge to the effective treatment of S. aureus infections [13]. Government health
policies and the health care systems in which they are implemented play a crucial role in determining the efficacy of
interventions to contain antimicrobial resistance. Some of the challenges are difficulty in Strengthening of
Surveillance, Data Standard Operating Guidelines, and Improvement in antibiotic prescription practices, over the
counter sale of antibiotics, Poor sanitation, endemic infections, malnutrition, Limited public awareness and
government commitment and timeline, Lack of coordination and fragmentation of effort [12, 10].
The appearance of resistance to antibiotics is a direct consequence of antibiotic effect and use, the rising
prevalence of antibiotic resistance, which is due to the selective pressure exerted by these many
Drugs [21, 21, 22] . The evidence for this has been summarized [32] in the five following well-documented
observations, Changes in antimicrobial use are paralleled by changes in prevalence of resistance. Increasing duration
of antibiotic treatment of patients is associated with increasing rates of colonization with resistant organisms.
Antimicrobial resistance is more prevalent in nosocomial than community-acquired strains [21].The areas of highest
antibiotic use in hospitals have the highest rates of resistance. During nosocomial outbreaks, patients with resistant
strains have received antibiotics more often than have controls.
3. STRATEGIES
Educational and awareness program for communities and different categories of health care professionals.
There should be an integrated approach between provider and consumer sides to effectively prevent the
antimicrobial resistance. The implementation of national efforts to prevent and contain antimicrobial resistance
should be through a multi-sectorial national steering committee headed by the senior-most health executive and
facilitated through advisory or expert groups [27]. From the side of policy makers, contriver, practitioners and
prescribers, pharmacists, dispensers, institution managers, diagnostic and pharmaceutical industries, department of
animal husbandry and from the consumer side patients and community is important in this regard.Strengthen
communicable diseases control program to reduce disease burden and accord priority to the discipline of infectious
diseases in medical education and health services. Constructive interactions with the pharmaceutical industry for

4. International Journal of Research In Science & Engineering e-ISSN: 2394-8299
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ensuring appropriate licensure, Conduct of operational research for better understanding of the technical and
behavioral aspects of prevention and control of antimicrobial resistance, regulate and promote rational use of
medicines and ensure proper patient care at all levels
3.1 Summary
Antibiotics have always been considered one of the curious discoveries of the 20th century. This is true, but the
real marvel is the rise of antibiotic resistance in medical institution, communities, and the environment consequent
with their use.There are many pathogens that are resistant to many antibiotic category, and infections make by
multidrug resistant (MDR) organisms are limiting treatment options and compromising effective therapy. Antibiotic
resistance occurs when it is concerned with the progress, acquired and spread of the resistance gene itself.To achieve
complete restitution of therapeutic applications of antibiotics, there is a necessary for more information on the role
of environmental micro biomes in the rise of antibiotic resistance, mitigation of antimicrobial resistance is therefore
necessary, and requires that many health professionals understand antibiotic sensitivity and resistance at the many
population, organism, cellular and molecular levels.This review presents the closest aspects of antibiotic resistance
development over a years ago, with the conclusion that it is time to act.
3.2 Acknowledgement
We thank all the friends of our university who support in our studies and also for their valuable contribution of
time. We thank to Mr.Kiran Sapkota for valuable and cogent idea.
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