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PATHOGENS AND
ISSUES IN
PHARMACOLOGY
Jassin M. Jouria, MD
Dr. Jassin M. Jouria is a medical doctor,
professor of academic medicine, and medical
author. He graduated from Ross University School of Medicine and has completed his
clinical clerkship training in various teaching hospitals throughout New York,
including King’s County Hospital Center and Brookdale Medical Center, among others.
Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep
tutor and instructor for Kaplan. He has developed several medical courses and
curricula for a variety of educational institutions. Dr. Jouria has also served on
multiple levels in the academic field including faculty member and Department Chair.
Dr. Jouria continues to serves as a Subject Matter Expert for several continuing
education organizations covering multiple basic medical sciences. He has also
developed several continuing medical education courses covering various topics in
clinical medicine. Recently, Dr. Jouria has been contracted by the University of
Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-module
training series for trauma patient management. Dr. Jouria is currently authoring an
academic textbook on Human Anatomy & Physiology.
ABSTRACT
Antibiotic therapy, as part of a medical plan and lifesaving measure is
a primary focus in terms of the general principles that clinicians must
understand when selecting a course of pharmacology treatment for an
infectious disease. This course is part of a 2-part series on
antimicrobial therapy with a focus on general issues affecting antibiotic
selection, the types of pathogens and diseases treated, and on specific
antibiotics’ indication, administration and potential adverse effects.
Antibiotic misuse and resistance is discussed.
Policy Statement
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This activity has been planned and implemented in accordance with
the policies of NurseCe4Less.com and the continuing nursing education
requirements of the American Nurses Credentialing Center's
Commission on Accreditation for registered nurses. It is the policy of
NurseCe4Less.com to ensure objectivity, transparency, and best
practice in clinical education for all continuing nursing education (CNE)
activities.
Continuing Education Credit Designation
This educational activity is credited for 5 hours. Nurses may only claim
credit commensurate with the credit awarded for completion of this
course activity.
Pharmacology content is credited for 1 hour.
Statement of Learning Need
The health literature has identified the inappropriate use of
antimicrobial agents, as well as the evolving pathogenicity of bacterial
organisms and rising problem of antimicrobial resistance. This is a
critical learning topic for health clinicians, especially in the field of
infectious disease as decisions are made to treat and educate patients
to prevent and address an infectious disease process.
Course Purpose
To provide clinicians with knowledge of issues in antibiotic
pharmacology and related preventive and life-saving measures.
Target Audience
Advanced Practice Registered Nurses and Registered Nurses
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(Interdisciplinary Health Team Members, including Vocational Nurses
and Medical Assistants may obtain a Certificate of Completion)
Course Author & Planning Team Conflict of Interest Disclosures
Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA,
Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures
Acknowledgement of Commercial Support
There is no commercial support for this course.
Please take time to complete a self-assessment of knowledge,
on page 4, sample questions before reading the article.
Opportunity to complete a self-assessment of knowledge
learned will be provided at the end of the course.
1. A pathogen can broadly be defined as a
a. bacteria that invades the body.
b. viral infection.
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c. microorganism that has the ability to cause disease.
d. bacterial infection.
2. True or False: Lactobacilli help the body destroy pathogens
that make their way into the digestive system.
a. True
b. False
3. Potential ways that antibiotics interact with contraception
pills is
a.
b.
c.
d.
in the acidic environment of the stomach.
in the liver during metabolism.
normal flora in the bladder.
normal flora in the lower lung.
4. _________ refers to a classification for the duration of
pathogens.
a.
b.
c.
d.
Communicable
Aerobic
Chronic
Zoonotic
5. Antibiotic resistance is a natural phenomenon caused by
a. the failure of patients to take their antibiotics as prescribed.
b. the bacterial genome or genetic component constantly
improves and changes with time.
c. the failure of patients to seek medical treatment as soon as the
infection symptoms appear.
d. healthcare personnel prescribing the wrong antibiotics.
Introduction
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Infectious diseases are responsible for approximately one-third of all
fatal cases in the world, as against cancers and other medical
conditions. In addition to ancient, life-threatening infectious diseases,
such as tuberculosis and malaria, new infectious diseases are
constantly emerging, which include diseases like AIDS (acquired
immune deficiency syndrome), Avian flu, Swine flu, etc. These have
already led to the death of 25 million people worldwide. To add to
these woes, some diseases which were earlier thought to be the result
of a cause other than bacterial infection are now thought to have a
bacterial infection cause; for example, most gastric ulcers were
believed to be caused by stress or spicy food, but now it has been
proven that it is because of bacterial infections of the stomach caused
by Helicobacter pylori. Also, infectious diseases are not spread equally
across the planet and economically backward and poorer countries and
communities suffer more as compared to developed countries. This is
because of poor public sanitation and public health systems, lack of
knowledge among the masses, which are further compromised by
natural disasters or political upheavals. Some infectious diseases,
however, occur exclusively between industrialized communities like
Legionnaire’s disease that commonly spreads through air conditioning
systems.
Pathogens
Health scientists have long been both troubled and fascinated with
infectious diseases. The earliest written descriptions of how to limit the
spread of rabies date back more than 3,000 years. Since the middle of
1800s, physicians and scientists have struggled to identify the agents
that cause infectious diseases, collectively termed as pathogens. More
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recently, the advent of microbial genetics and molecular cell biology
has greatly enhanced our understanding of the causes and
mechanisms of infectious diseases. It is now known that pathogens
frequently exploit the biological attributes of their host’s cells in order
to infect them. This understanding has provided new insights into
normal cell biology, as well as strategies for treating and preventing
infectious diseases.1
Pathogens are generally referred to as an invader that attacks the
body. However, in reality, a pathogen, like any other organism, simply
tries to live and procreate. A pathogen lives at the expense of the host
organism, which is rich in nutrients, provides a warm, moist
environment, and a constant temperature in which the organism can
dwell and easily multiply. It is very convenient for many organisms to
evolve and reproduce in such a favorable environment and so it is not
surprising that every individual acquires some kind of infection.1,2
What Is a Pathogen?
A pathogen can be defined as a microorganism that has the ability to
cause disease. Since a pathogen is a microorganism that can cause
pathological damage in a host, this immediately raises the question:
What is it about the microorganism that enables it to cause disease or
produce damage or how does a microorganism cause damage to the
host?
In the 19th century, when germ theory was discovered, many of the
major pathogenic organisms were encapsulated or toxigenic bacteria,
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and this suggested that there were inherent variations between
pathogenic and non-pathogenic microbes; however, an organism could
be attenuated in the laboratory, but virulence may be restored the
moment it enters the host. Given this fact, it is obvious that a clear
classification is problematic since a microbe may exist in pathogenic
and non-pathogenic states.3
Types of Pathogens
Pathogens are overabundant because they will simply survive
anywhere. Most thrive in heat, whereas others prefer the cold. Some
species need oxygen or human host, i.e., aerobic bacteria, whereas
others do not, i.e., anaerobes. Pathogens that cause communicable
diseases can be classified into different types based on multiple
characteristics as follows.
Route of Transmission
Route of transmission in one-way pathogens can be categorized.
Differing types of pathogens can infect by more than one route. Routes
of transmission are highlighted below.7
 Food born: botulism, E. Cole, camphylobacter, shigella,
norovirus, Listeria, toxoplasmosis, salmonella, etc.
 Waterborne: Cholera, rotavirus, adenoviruses, shigella,
enteroviruses, giardia.
 Air born: Rhinovirus, coxsackievirus, respiratory syncytial virus,
parvovirus B19, coronavirus, parainfluenza.
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 Vector born: (vector can be fleas, flies, ticks, mosquitoes) Yellow
fever, Lyme disease, dengue, malaria, plague, tularemia,
Chagas disease, Rocky Mountain Spotted Fever.
 Blood born: hepatitis B virus, HIV
 Zoonotic: Leptospirosis, rabies, cat scratch disease, brucellosis,
dermatophytosis.
 Transmitted from another person like sexual transmitted
diseases (STDs).
Duration of Infection
Another classification for various kinds of pathogens is how long the
infectious disease lasts. Most infections constitute three major types:
 Acute
 Latent
 Chronic
Some species of pathogens can be extremely infectious and hence
require special handling. A few of the different types of diseases that
are distinctive include:
 Lassa fever
 SARS
 Nipah virus encephalitis
 Ebola hemorrhagic fever
 Hantavirus pulmonary syndrome
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Newer studies are now showing that there might be links between
different types of pathogens to cardiovascular disease, diabetes, some
cancers, multiple sclerosis, and various chronic lung diseases. But not
all germs are considered pathogenic. In fact, some are essential for
health, such as lactobacillus, bacteria that are present in our intestinal
flora. Lactobacilli help the body destroy pathogens that make their way
into the digestive system.4
Recognized human pathogens can be classified as:
 Viruses
 Bacteria
 Fungi
 Protozoa
 Helminths
A wide range of pathogens infects humans. There are 1,407
pathogenic species of viruses, bacteria, fungi, protozoa, and helminths
that are presently recognized.5
Pathways
Pathogens have developed a specific mechanism for interacting with
their hosts (the human body), a complex and thriving ecosystem.
There are about 1013 types of human cells and also approximately
1014 bacterial, fungal, and protozoan cells, inside a complex human
body. These thousands of types of microbes exist inside the human
body as normal flora, and are typically bound to certain parts of the
body, including the mouth, nose, skin, large intestine, and vagina. The
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normal flora is not simply freeloading inhabitants of the normal human
body; they do affect human health. The anaerobic bacteria that are
present in the intestines contribute to the digestion process of food,
and also play a role in the correct development of the gastrointestinal
tract in infants. Other normal flora present on the skin and other parts
of the body also prevent infectious diseases by competing with disease
causing microorganisms for nutrients and space. In other words,
people are continually infested with pathogens, the vast majority of
which seldom become noticeable.
If it is normal for humans to live in such close intimacy with such a
wide range of microorganisms, why is it that some organisms are
capable of damaging the normal cells and producing various diseases
or even causing death? The ability of a specific organism to cause
obvious harm and illness in a host will rely greatly on external
influences.
Primary Pathogens
Primary pathogens, which cause illness in most healthy human beings,
are typically distinct from the normal flora. They are different from
commensal microorganisms in their ability to breach barriers and
survive in host locations where normal microorganisms cannot. Normal
microorganisms cause problems only if the immune system is
weakened or if they gain access to a sterile part of the body; for
example, peritonitis, where a bowel perforation enables gut flora to
enter the peritoneal cavity of the abdomen, or where the immune
response to flora is unsuitably sturdy and allows an issue to occur.
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Notably, primary pathogens do not require an immune-compromised
or injured host. Primary pathogens have developed extremely
specialized mechanisms for crossing cellular and biochemical barriers
and for eliciting specific responses from the host organism that
contribute to the pathogen’s survival and multiplication. For a few
pathogens, these mechanisms are adapted to a specific host species,
whereas for most pathogens, they are sufficiently general that they
can invade, survive, and thrive in a wide range of hosts. Some
pathogens cause acute epidemic infections and have a tendency to
spread rapidly from one sick host to another; historically, important
examples are the smallpox and bubonic plague. Others cause
persistent infections, which will last for several years in a single host
without necessarily leading to overt disease, and examples include
Epstein Barr virus, Mycobacterium tuberculosis and Ascaris. Though
each of these pathogens can develop into a critical illness in some
individuals, billions of individuals who are principally unaware that they
are infected can carry these pathogens in an asymptomatic way.
Protection Against Infection
A thick and quite tough covering of skin protects most parts of the
human body from the environment. Pathogens have to cross the
protective barriers to colonize the host cell. The first step in infection is
for the pathogen to colonize the host. Pathogens that colonize the
protective epithelial layer must be able to avoid clearance by the host
cell. Hitching a ride through the skin with the help of an insect
proboscis is just one of the strategies pathogens commonly use to go
through host barriers. Whereas, several human tissue barriers like the
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skin and also the lining of the mouth, an enormous internal organ, are
densely inhabited by normal flora. Additionally, the lining of the small
intestine, the lower lung and the bladder, are usually kept nearly
sterile despite the presence of a comparatively direct route to the
external environment.
A layer of protective mucus secretion covers the respiratory
epithelium, and the coordinated movement of respiratory cilia sweeps
away the mucus and trapped bacteria and debris up and outside the
lungs. The host epithelial cell lining of the upper gastrointestinal tract
and in the urinary bladder also has a thick layer of mucus, and these
microorganisms are periodically flushed by peristalsis and by voiding,
respectively. The infective bacteria and parasites that manifest in these
epithelial surfaces have developed some specific mechanisms for
overcoming this host defense mechanism of frequent cleaning. For
example, those that infect the urinary tract, have the ability to resist
the washing action of the bladder by adhering tightly to the epithelium
lining of the urinary tract through specific proteins or protein
complexes that recognize and bind to host cell-surface molecules
(called adhesion).
Intracellular pathogens have various mechanisms for both entering a
host cell and leaving it. Various extracellular pathogens such as B.
pertussis and V. cholerae cause infection in their host without entering
the host cells. However, most others, including all viruses and various
bacteria and protozoa are intracellular pathogens. Their preferred
place for survival and replication is within the cytosol or intracellular
area of particular host cells. This kind of pathogen attack strategy has
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numerous advantages. These intracellular pathogens are not exposed
to antibodies produced by the host and thus are not easily targeted by
phagocytosis. Also, the added advantages are that they are bathed in
a rich source of many nutrients like sugars, amino acids, and other
nutrients present in host cell cytoplasm. To acquire this lifestyle,
however, the pathogen requires the development of mechanisms for
entering host cells, and find a suitable subcellular niche where it can
survive and replicate, and for exiting from the infected cell to spread
the infection.
Viruses and bacteria carry out the intracellular movement by using the
host hell cytoskeleton. The cytoplasm of human host cells is extremely
viscous. It is filled with organelles along with networks of cytoskeletal
filaments, which inhibits the diffusion of particles the size of a
bacterium or a viral capsid.1 In order to survive and multiply while
living in a host, a pathogen must be able to:1,2

Colonize the host

Find a nutritionally compatible place in the host’s body

Avoid, subvert, or circumvent the host’s innate and adaptive
immune responses

Replicate, using host resources

Exit and spread to a new host
Underneath severe selective pressure to induce host responses that
facilitate to accomplish these tasks, pathogens have evolved
mechanisms that maximally exploit the biology of their host
organisms.
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In present times, humans have reduced the chance of getting
infections by deliberately altering our behavior, which has decreased
the ability of pathogens to infect us. Enhancements in public health
measures, including the construction of working sewer systems and
clean water supplies, have facilitated the gradual decrease in the
frequency of total fatal cases due to infectious diseases over the past
decades. Societies that have contributed resources to improve child
nutrition have benefited from generally improved health, including
greatly reduced death rates from early childhood infections. Medical
interventions like antibiotics, vaccinations and routine testing of blood
before transfusion, have also markedly reduced infectious diseases in
humans.1,2
Pathogens that cause illness in humans are phylogenetically different.
The most common are viruses and bacteria. Viruses cause infectious
diseases ranging from autoimmune deficiency syndrome (AIDS) to
smallpox to the common cold. They are fragments of nucleic acid (DNA
or RNA) encoding a comparatively few number of gene products
wrapped in a protective shell of proteins and membrane. They do not
have the capacity of carrying out an independent metabolic activity
and thus rely completely on metabolic energy provided by the host.
Viruses vary in their size, shape, and content and the same holds true
in cases of various other pathogens. The flexibility to cause various
illnesses is an evolutionary niche, and not an inheritance shared
among close relatives. All viruses use the protein synthesis mechanism
of their host cells for their replication, and also most of them depend
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on host cell transcription machinery whereas, of all the bacteria, very
few are primary pathogens. They are much larger and more complex
than viruses. Bacteria are free-living cells, which can perform basic
metabolic functions by themselves, and rely on the host cells primarily
for nutrition.
Some infectious organisms are eukaryotic. They vary from a single
celled fungus and protozoa to a large, complex metazoan like parasitic
worms. Some rare neurodegenerative diseases are caused by an
unusual type of infectious particle known as a prion, which is made
only of protein. Though the infectious particle prion contains no
genome, it can even replicate and kill the host. There is striking
diversity within each class of pathogen. Every individual organism
causes illness by completely different means and the same organism
can also cause different types of illness in different hosts, making it
more difficult to understand the basic biology of infection. In the
following sections the basic features of transmission of disease by each
of the major types of pathogens will be discussed.1,2
Bacterial Transmission Of Infection
Bacteria are small in size and appear to be structurally simple. Most
are often broadly classified by their form or shape like sphere shape,
rods or spirals, and can also be classified by their gram staining
properties (negative or positive). In spite of their comparatively
smaller size and simple range of shapes, they have extraordinary
molecular and metabolic diversity. At the molecular level of actions,
they are far more diverse than eukaryotes, and they can successfully
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occupy ecological places in extremes of temperature and with nutrient
limitations that may restrain even the foremost intrepid eukaryote.1
The qualities by which pathogenic bacteria cause transmission of
disease are broadly divided into two types:
1. Invasiveness:
As the name suggests, it is the ability to invade tissues. It is
comprised of mechanisms for colonization, production of
invasins, which are extracellular substances that facilitate
invasion and the threshold to bypass or overcome the host
immune response or defense mechanisms.
2. Toxigenesis:
It is the ability to produce toxins. Bacteria manufacture two
types of toxins called exotoxins and endotoxins.
Bacterial Colonization
The first step of microbial infection is colonization; at the appropriate
portal of entry the pathogen establishes itself. Bacteria commonly
colonize host tissues that are in frequent contact with the external
environment. The most common sites for colonization include the skin,
digestive tract, the respiratory tract, urogenital tract and the
conjunctiva. Organisms that cause infection in these regions have
developed tissue adherence mechanisms and the threshold to
overcome or ability to withstand the constant pressure of the host
immune defense mechanism.
Bacterial Adherence to Mucosal Surfaces
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In the simplest type of bacterial adherence to a eukaryotic cell or
tissue surface, bacteria need the involvement of two factors: a
receptor and a ligand. The receptors are defined as specific
carbohydrate or peptide residues on the eukaryotic cell surface. The
bacterial ligand also known an adhesin and is typically a
macromolecular component of the bacterial cell surface that interacts
with the host cell receptor. Receptors and adhesins typically interact in
a specific complementary way.
Mechanisms of adherence to cell or tissue surfaces involves two steps:
1. Nonspecific adherence It is a reversible attachment of the bacteria to the eukaryotic
surface (sometimes referred as "docking").
2. Specific adherence It is an irreversible and permanent attachment of the bacteria to
the surface (sometimes referred to as "anchoring").
Commonly, it is seen that nonspecific adherence or reversible
attachment precedes specific adherence or irreversible attachment.
However, in some cases, the reverse situation occurs or sometimes
specific adherence never occurs.
Evasion of Host Defenses
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Some pathogens have the ability to resist the bactericidal components
produced by the host defense mechanism. In gram-negative bacteria,
the outer membrane is a formidable permeability barrier, which is not
easily penetrated by hydrophobic compounds like bile salts that are
otherwise harmful to the bacteria. Pathogenic mycobacteria have a
waxy cell wall, which has the ability to resist the attack or digestion
caused by most of the tissue bactericides. Intact lipopolysaccharides
(LPS) of gram-negative bacteria's may protect the cells from the action
of lysozyme.
Overcoming Host Phagocytic Defenses
Bacteria that invade tissues are firstly exposed to phagocytes. It is
seen that bacteria, which readily attract phagocytes and that are easily
ingested and killed by them, are not successful as a parasite, and
bacteria that are successful in interfering with the activities of
phagocytes or in some way avoid their action are established as
parasites. The strategies used by bacteria to avoid or attack
phagocytes are numerous and diverse, and typically aim at blocking
one or more steps in the phagocytic action. The steps in phagocytosis
include:6

Contact between phagocyte and microbial cell

Engulfment

Phagosome formation

Phagosome lysosome fusion

Killing and digestion
Toxigenesis
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Exotoxins are discharged from bacterial cells and may act at tissue
sites far from the position of the bacterial growth. Endotoxins are cellassociated substances that refer to lipopolysaccharides, which are
components of the outer membrane of gram-negative bacteria.
However, endotoxins can also be discharged by the growing bacterial
cells and cells that are attacked or destroyed by effective host defense
or by antibiotics. Hence, these two types of toxins, both soluble and
cell-associated, can be carried by blood and lymph and they cause
cytotoxic effects at tissue sites remote from the bacterial growth.6
Viral Transmission Of Infection
All aspects of viral transmission depend upon host cell mechanism.
Even as intracellular pathogens, they use their own machinery for DNA
replication, transcription and translation and they provide their own
sources of metabolic energy. Viruses carry their own information in the
form of nucleic acid. The information is replicated, packaged, and
preserved by the host cells. Viruses have a small genome, which
comprises of either DNA or RNA (a single nucleic acid type), and may
be single or double stranded. The genome is covered in a protein coat,
which in some viruses is further covered by a lipid envelope. Viruses
replicate in numerous ways.
The first step for any intracellular pathogen is to bind to the surface of
the host target cell. Viruses accomplish this binding through the
association of a viral surface protein with a specific receptor on the
host cell surface. Of course, no host cell receptor evolved for the sole
purpose of allowing a pathogen to bind to it; these receptors all have
other functions. Virions (single virus particles) enter host cells by
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membrane fusion, pore formation, or membrane disruption. After
recognition and attachment to the host cell surface, the typical next
steps for a virion is to enter the host cell and release its nucleic acid
genome from its protective protein coat or lipid envelope. In most
cases, the liberated nucleic acid remains complicated with some viral
proteins. Enveloped viruses enter the host cell by fusing either with
the plasma membrane or with the endosomal membrane following
endocytosis.
A virion that attacks a single host cell can reproduce thousands of
progeny in the infected cell. Because of this prodigious multiplication,
it often kills the host cell. Thus, causing lysis of the host cell or the
infected cell breaks open thereby allowing the progeny virions access
to nearby host cells. Most of the clinical manifestations of viral
infection show this kind of cytolytic effect of the virus. For example,
lesions caused by the smallpox virus and the cold sores formed by
herpes simplex virus both reflect the attacking and killing of the
epidermal cells in a local area of infected skin. In general, replication
involves disassembling infectious virus particles, replication of the viral
genome, synthesis of the viral proteins by the host cell translation
machinery and reassembly of these components into progeny virus
particles.
As discussed earlier, in some cases host cell death is also caused as a
result of the immune responses to the virus. Virions come in numerous
shapes and sizes and they cannot be systematically classified by their
relatedness into a single phylogenetic tree. The capsid that covers the
viral genome can be composed of one or several proteins, arranged in
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specific repeating layers and patterns; the viral genome together along
with the capsid is known as a nucleocapsid. In enveloped viruses, the
nucleocapsid is covered by a lipid bilayer membrane, which the virus
gains in the process of growing from the host cell plasma membrane.
Hence, in cases of enveloped virus, they leave the cell by budding,
without damaging the plasma membrane and without killing the cell
but, in cases of non-enveloped viruses, they commonly leave an
infected cell by lysing it. Because of this mechanism, an enveloped
virus can cause chronic infections that may last for years, often
without noticeable effects on the host.
In addition to this variety, all viral genomes encode three types of
proteins: proteins used for replicating the genome, proteins used for
packaging the genome and helping in delivering it to more host cells,
and proteins which help in modifying the structure or function of the
host cell to enhance the replication process of the virions. Many of the
viral genomes also encode the fourth type of proteins, which modulate
the host’s normal immune defense mechanisms.
As the host cell’s machinery performs most of the essential steps in
viral replication, the identification of effective antiviral medicine is a
great challenge. For example, antibiotic tetracycline specifically attacks
bacterial ribosomes, but as viruses use the host cell’s ribosomes to
make their proteins, it is difficult to find a drug that specifically attacks
viral ribosomes. The best strategy for stopping the transmission of
viral diseases is to prevent them by vaccination; for example,
eradication of smallpox and poliomyelitis.1,2
Fungal And Protozoan Transmission Of Infection
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Fungal and protozoan parasites have complicated life cycles with
multiple forms. Many of the pathogenic fungi and protozoa are
eukaryotes and therefore it is more difficult to find a drug that will kill
the pathogen without killing the host. As a consequence, antifungal
and antiparasitic drugs are often less effective and more toxic than
antibiotics.
A second characteristic of fungal and parasitic infections that makes
them tough to treat is the ability to switch between various different
forms during their life cycles. A drug that is effective at killing one
form is often ineffective at killing another form, which therefore
survives the treatment. The fungal branch of the eukaryotic kingdom
includes both unicellular yeasts (such as, Schizosaccharomyces pombe
and Saccharomyces cerevisiae) and filamentous, multicellular molds
(like those found in moldy vegetables, fruit or bread).
Most of the important pathogenic fungi exhibit dimorphism; which is
the flexibility to grow in either yeast form or mold form. The transition
of yeast to mold or mold to yeast is usually associated with infection.
For example, Histoplasma capsulatum, grows as a mold in the soil at
low temperature, but when inhaled into the lung it switches to yeast
form, wherein causing the disease histoplasmosis.
Protozoan parasites are single celled eukaryotes with elaborate life
cycles as compared to fungi, and they often require the service of
more than one host. The most common example is Plasmodium, which
causes Malaria, which infects more that 200-300 million people every
year and causing death in 1-3 million of them. They are transmitted to
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humans by the bite of the female of any species of the Anopheles
mosquito.
Virulance
Interaction of microbes and host leads to virulence. Medically,
virulence can be defined as the ability of an organism to invade the
tissues of a host and produce the disease. It is a measure to
determine how dangerous a pathogen is and to compare how
aggressive different pathogens or organisms may be. This can be
judged from the fatality rates and records, which show how many
people fell sick by the various strains of microbes.
Virulence helps to differentiate pathogens from non-pathogens. A
number of factors can influence the ability to cause disease, which
includes the genetic makeup of both the microbe and host. Virulence
and the factors associated with it is a controversial topic in the field of
medical science as well as evolutionary studies of microorganisms. The
theory8 of microbial disease still does not clearly define the term
virulence, which still creates confusion amongst students.
Virulence and virulent are both derived from the Latin word virulentus
which means “full of poison.” Currently, virulence is simply known as
the capacity of an organism to produce the extent of the disease and is
conventionally a characteristic of a microbe. Thus, this concept of
virulence helps to broadly understand the pathogenesis of the disease
as well as compare various pathogens. Virulence is not an independent
variable, but remains heavily dependent upon the host resistance as
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well as the interaction of microbe and host, and thus cannot be solely
known as a microbial characteristic.
Reduction in host defenses, which is dependent upon numerous
variables, is defined as pathogenic virulence. Virulence is a complex
and dynamic phenomenon that varies according to both host and
microbial factors. This phenomenon depends upon other exogenous
factors such as medical intervention too.
A functional aspect of pathogenicity is virulence. It is an important
clinical term, which means that host damage indicates disease.
Through studies and trials we hope to underline the characteristics of
virulence and quantify the amount of host damage caused by the
disease.
Terminology of Pathogen and Virulence
Virulence and pathogenicity are commonly overused terms amongst
microbiologists that are rather difficult to replace and clearly
demarcate.9 Although in experimental situations many variables can
be controlled and maintained, many variations still tend to occur. The
genetic variation and diversity amongst both the hosts as well as the
microbes has lead to a wide variety of host microbe interactions. The
high transmission rates and low recovery rates of hosts enable
persistence of pathogens amongst host populations. This also affects
the outcome of virulence amongst many microbes.
Attributes of Virulence
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Since virulence is recognized as a multifaceted characteristic of some
microbes, it is necessary to focus on the attributes of virulence.10
Virulence was earlier characterized by microbe properties, the extent
of pathogenicity, ability to put down host defenses, and invasive
power, which includes the level of infectivity and the rate of
multiplication and proliferation in the host body.
Toxicity
The amount of poisonous substances released from microbes
influences the level of virulence. This was one of the earliest theories
of the twentieth century. Toxicity was defined as the amount of toxins
or poison produced by the microbes. Classification of toxins produced
by the bacteria depended upon their immunogenicity and their
capacity to produce antitoxins. Four types of bacterial toxins were
identified, namely, ptomaines produced by decomposition, exotoxins,
endotoxins made after the death of the microorganisms and the
bacterial proteins. Thus, definition of toxicity was further modified and
redefined as the capacity and extent to which the toxins can invade
and damage the host tissue, which was not only restricted to
poisonous toxins, but included damage as a result of metabolic end
products, certain allergic products produced by the microbes, and the
nutritional status of the host.
Aggressiveness
The way the pathogens invade, survive and multiply was another
attribute of virulence known as aggressiveness. Though toxicity and
aggressiveness were coined differently, occasionally both these
attributes were mixed as there are many toxins produced by
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microorganisms that influenced the way they invaded, survived and
multiply. For example, microbe Staphylococcus aureus produced toxins
known as leucocidins that damaged host leukocytes cells. Certain
microbes clearly showed that most of these attributes were clearly
different, such as, Streptococcus pneumoniae was severely aggressive
but not very toxic. Thus, any factor that promoted the organism to
grow or multiply would also be responsible for the aggressiveness.11
Replication And Transmission
Replication and transmission are both equally important for microbes
to persist in their hosts along with their contagiousness. The ability of
organisms to multiply and survive in their host’s environment has been
characterized as an attribute of virulence. These factors such as
contagiousness and transmission are still very complex in their
relationship to virulence of organisms. Many still do not clearly
recognize these as definite attributes of virulence, as there are many
organisms that can cause life-threatening conditions, but are
absolutely non-contagious.
Adherence and Attachment
Another essential attribute for microbial virulence is host adherence.12
Certain characteristics present in microbes encourage adherence to
mucosal surfaces. However, certain microorganisms in spite of
adherence to mucosal surfaces are not very virulent.
Antigenic Variation
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There are selected ways, by which microbes can adapt in order to
avoid selective pressures of the host. Many strains of microbes become
resistant to serum during infection. Thus, antigenic variation can
increase the fitness of microbes by allowing the microbe to survive in
the host environment.
Immunologic Variations
Some microbes can cause detrimental immune responses that are
attributed to its virulence. Thus, hypersensitivity was equally
important for invasiveness. Reactions such as intense cellular reaction
and tissue destruction in tuberculosis all show the virulence of these
microbes.
Evolution of Virulence
According to studies in evolution, virulence tends to increase in
transmission between non-relatives rather than between parent-tochild. This happens as the fitness of the host is bound in vertical
transmission but not in horizontal transmission.13
Virulence will differ amongst species, subspecies as well as different
strains. A better understanding of the many virulence factors can
provide a lot of help in the field of therapeutics. We can name and
classify different pathogens on the basis of their virulence factors.
Concept of Virulence Factors
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This concept of virulence14 factors focuses on the microbe-induced
effects on the health status of the host. The capacity of an organism to
cause disease in the host is related to the expression of a microbial
characteristic. Thus virulence factors have been defined as factors that
affect virulence when not presented, but not viability. These factors
have multiple roles including promotion of microbial adherence,
invasion as well as enhancing growth of microbe in the host. They also
inhibit phagocytosis and control intracellular survival. To sum up,
virulence factors involve:15

Colonization (by invasion) and attachment in host cells
(adherence)

Avoiding host immune responses (capsule formation)

Suppression of the host immune system

Get nutrition from the host

Entry and exit out of the cells
Identification of Virulence Factors
The idea that virulence factors are microbial characteristics that
influence the ability and capacity of virulence has lead to several
investigations of microbial pathogenesis. Many studies show that
certain microorganisms16 have pathogenicity islands as well as some
lysogenic bacteriophages that provide the virulence ability of the
bacteria.
Recently, genetic studies were conducted to study and identify the
genes that control such traits and characteristics, which affect and
regulate virulence in these pathogens. Understanding these virulence
factors is also being used as a means to control infection. Three of the
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common ways to analyze and understand these factors are
biochemically, immunologically and genetically.17
Limitations of Virulence Factors
For many pathogens, virulence factors have not been identified.
Though virulence is conferred by virulence factors in pathogens,
especially in microbes that are free living and attack, the host’s
immunity may be intact. However, this cannot be applied to many
microorganisms that can cause disease in immunocompromised
individuals such as C. albicans and Mycobacterium tuberculosis. The
factors required for survival in host and microbial replication can be
considered as virulence factors.
While this goes against the conventional definition of virulence
factors18 for certain viruses, it is difficult to state virulence factors
according to definition (as replication in hosts is considered as
pathogenicity). In spite of all the confusion associated with the
definition, it is generally agreed that irrespective of whether they are
needed for growth or are physiologically a part of the microbe that can
damage, the host confers virulence.
Virulence Influenced by Host Factors
Any interference or change in host defenses can affect the virulence of
many microbes. Certain microbial characteristics that encourage and
cause disease in the absence of host defense mechanisms show that
virulence factors may not even be recognized as these microbes would
be avirulent in normal healthy hosts. So a reduced antibody reaction
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can encourage virulence, while a normal antibody response would elicit
no or highly reduced virulence in the host. Certain intrinsic factors
present in the host can also modify virulence. With the emerging
antigenic variants, it can provide virulence to many microbes even
amongst immunized individuals. This clarifies that virulence includes
attributes of both, host as well as microbe.
Measuring Virulence
Virulence is usually measured by the ability of an organism to produce
disease in an animal. This was concluded after studying that the
amount of inoculum that was needed to kill an animal after an
experimental infection differed from microbe to microbe. As a result,
virulence was inversely proportionate to the number of
microorganisms required to cause an infection. Thus, a standard for
measurement later on became the smallest inoculum needed to kill an
animal. There were many limitations associated with this technique of
measuring virulence. The route of transmission was also an important
variable while measuring the virulence. These methods of measuring
virulence are inadequate and there is no absolute value of virulence.
Virulence is always relative. This broadens the understanding of the
differences amongst various microbes in causing diseases.
The complex phenomenon of virulence is universally accepted.19
Whether it is a characteristic of a microbe or a virulence factor still
remains a controversy. Virulence is an intensely complex and integral
part that is dependent upon both the host as well as a microbe.
Though it has been stated that virulence factors separate pathogenic
from nonpathogenic microbes, it cannot be universally acknowledged.
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This does not explain the fact that certain avirulent microbes can affect
immune-compromised hosts. Host damage occurs due to both
microbial as well host processes and cannot be attributed due to
virulence.
Newer investigations that focus on the host as well as microbial
contributions and interactions help to better understand the concept of
virulence. We cannot concentrate on single entities, but need to
consider the host microbe interactions to regulate virulence. Further
studies need to be conducted to understand the evolutionary pattern
of these microbes in order to illuminate an understanding of their
transmission rates as well as virulence factors.
Antibiotics
The invention of drugs that can fight bacterial infections has improved
the quality of life of humans. It has also contributed to the increase in
average life expectancy. Antibiotics have been one of the greatest
examples of drugs to fight bacterial infections. Antibiotics are widely
used all over the world by health care professionals in patients of all
ages. Apart from knowing the appropriate use of antibiotics, it is equal
or more important to know in which cases antibiotics should not be
used. These drugs need to be used rationally, keeping in mind their
advantages and limitations.
The right choice of an antibiotic also depends on various factors like
pharmacodynamics, interactions, and the patient’s immune status. The
indiscriminate use of these agents can turn out to be more harmful,
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making these valuable drugs useless. This course aims at giving a fair
idea about the uses of antibiotics in order to create an easily
comprehensible list of facts for practical use in the outpatient setting
as well as in hospitals.
The main aim of the use of antibiotics is to fight bacterial infections
and the choice of the antibiotic depends on multiple factors as detailed
below.
Mechanism
Bactericidal drugs kill the bacteria, which come within the sphere of
action of that particular antibiotic. Bacteriostatic drugs inhibit further
growth of bacteria. Though most of the treatments consist of
bacteriostatic variety of antibiotics, bactericidal drugs are used in
specific infections like complicated staphylococcal aureus infection and
in patients with altered immunity. The maximum level of
chemotherapeutic activity is attempted with antibiotics along with the
reduction in the toxicity to the host. The cell wall of bacteria is the
protective layer that prevents rupture of the cell owing to the
difference in the environmental osmolarity in relation to the host.
Antibacterial agents act by inhibiting the cell wall synthesis, by
disabling the peptidoglycan chain lining the cell wall.20 The antibiotics
that eventually result in the death of the bacterial cell are bacitracin,
glycopeptides, penicillin and cephalosporins. The inhibition of the
protein synthesis by way of binding to the 3OS subunit and 5OS
subunit of the bacterial ribosome leads to either bactericidal or
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bacteriostatic action depending on the antibiotic in use. The drugs that
act in this way are aminoglycosides, macrolides, chloramphenicol and
linezolid.21
Drugs like tetracycline and muciprocin also inhibit protein synthesis,
but by a little different action of blocking the binding of the isoleucine
tRNA synthetase and depleting cell stores. Drugs like sulphonamides
and trimethoprim inhibit bacterial metabolism by interfering with the
folic acid synthesis pathway that is necessary for all one-carbon
transfer reactions causing either cessation of the bacterial cell growth
or bacterial cell death. Quinolones, rifampin, nitrofurantoin and
metronidazole inhibit nucleic acid synthesis by hindering DNA gyrase
activity, making DNA replication impossible and thus limiting bacterial
growth.22
Pharmacokinetics
Pharmacokinetics refers to the level of the antibacterial agent that is
reached in the serum or tissue of the host following administration
over time. This is determined by the absorption, distribution,
metabolism, and elimination in the host, which are different for
different types of antibiotics. The bioavailability of a drug when
administered orally is less than when administered by intramuscular or
intravenous routes. Oral antibiotics are commonly used in the
outpatient setting owing to lower costs and easy patient acceptance.
Mild infections and a switch over from parenteral antibiotics call for the
use of oral antibiotics. Intramuscular (IM) injections show a 100%
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bioavailability, but are rarely used due to the pain they cause and are
mostly in use only in cases of long-term forms of penicillin and single
doses in acute otitis media. Intravenous (IV) administration provides
100% bioavailability and is most effective in severe infections requiring
hospitalization or when large doses are required.23 When infections are
located in areas where the reach of antibiotics is minimal or the site is
protected that makes penetration poor, i.e., cerebrospinal fluid,
prostate, eye, or cardiac vegetations, the use of parenteral antibiotics
for a prolonged period become necessary.
The elimination of antibiotics is mostly hepatic or renal, or may be a
combination of the two. Some antibiotics like rifampin, clarythromycin,
and cefotaxime have bioactive metabolites that contribute to the
efficacy of the action of the antibiotic. This is extremely important to
know in order to be able to select appropriate antibacterial therapy or
the adjustment of dosages in patients with impaired hepatic or renal
clearance.24,25
Choice of Antibiotic
A brief review of various antibiotics in reference to the spectrum of
bacteria that they treat is covered below.
Beta Lactams
Penicillins act against spirochetes, streptococci, E. faecalis, most
Neisseria and Clostridium. Ampicillin is effective against E. coli, Proteus
mirabilis, Shigella, Salmonella, and H. influenza. First generation
cephalosporins act against E. coli, Klebsiella and have poor activity
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against H. influenza. The second-generation cephalosporins have an
extended gram-negative spectrum against H. influenza, Neisseria, and
Proteus. Third generation cephalosporins have a broad-spectrum
gram-negative activity against Pseudomonas. Ceftriaxone has
excellent activity against Haemophillus, most S. pneumoniae strains,
and penicillin resistant Neisseria.
Vancomycin
Its action is limited to gram-positive bacteria and is usually chosen as
a second line of treatment for staphylococci, enterococci, and
streptococci infections. However, it is the drug of choice in infections
caused by Corynebacterium and methicillin resistant staphylococci.26
Aminoglycosides
This group of antibiotics has a limited action against gram-negative
bacteria and is not effective at all against anaerobic bacteria.
Aminoglycosides are the drugs of choice for severe upper urinary tract
infections with gentamycin and tobramycin being generally preferred.
However, the major disadvantage of the use of aminoglycosides is
their renal toxicity.
Macrolides
These antibacterial agents act against gram-positive bacteria and
Legionella, Chlamydia, Mycoplasma, Bordetella, and Campylobacter.
The antibacterial spectrum of clarithromycin and azithromycin is
similar to that of erythromycin. Clarithromycin is the drug of choice in
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the treatment of gastric H. pylori infection in combination with a
proton pump inhibitor.
Lincosamides
Clindamycin is the most widely used lincosamide owing to its broadspectrum activity against gram-positive and gram-negative anaerobes.
Bacteria resistant to erythromycin are also resistant to clindamycin. It
is the drug of choice for the treatment of severe, invasive, group A
streptococcal infections.
Chloramphenicol
Its use is limited to the treatment of typhoid fever, and is the drug of
choice in pneumococcal and meningococcal meningitis in patients with
severe penicillin allergy. It is rarely used in adult infections due to its
rare but dangerous side effect of irreversible bone marrow aplasia.
Tetracyclines
These antibiotics show bacteriostatic activity against gram-positive and
gram-negative bacteria causing various community-acquired infections
like chronic bronchitis, brucellosis, chlamydial infections, spirochetal
infections. Tetracyclines are also used in gram-positive infections like
syphilis, actinomycosis, leptospirosis and skin infections in patients
with penicillin allergy.27
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Sulphonamides
The bacteriostatic activity of this group of antibiotics by inhibition of
the folic acid synthesis pathway makes it effective against and is used
in the treatment of upper respiratory tract infections caused by S.
pneumoniae and H. influenza.
Fluoroquinolones
These have excellent activity against gram-negative rods and varied
activity against gram-positive cocci. Norfloxacin is not absorbed well
orally, but along with ciprofloxacin, levofloxacin, moxifloxacin, and
gatifloxacin are the drugs of choice in community-acquired pneumonia,
enteric fever, bacterial gastroenteritis, urinary tract infections and
other hospital-acquired gram-negative infections.
Rifampin
This drug is used in combination with other antibacterial agents in the
treatment of serious infections caused by methicillin-resistant
staphylococci.
Metronidazole
Its activity is limited against anaerobes and is the drug of choice in
treatment of anaerobes related abscesses in the lung, brain, or in the
abdomen.28 Metronidazole is also the drug of choice in the treatment
of bacterial vaginosis and antibiotic-associated pseudomembranous
colitis.
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Linezolid
This drug is specifically used in the treatment of infections caused by
E. faecium and E. faecalis. Linezolid is also used in infections caused
by staphylococci, enterococci, and streptococci.
Topical Antibiotics
Muciprocin is available only as a topical agent and is a drug of choice
for treatment of methicillin-resistant and methicillin-susceptible
staphylococci. Topical preparations also include sulfonamides,
bacitracin, neomycin, and novobiocin and are used in superficial skin
infections. These are also widely used in combinations as eye drops.
Antibiotics and Viral Infections
The very definition of antibiotics itself clearly states that these drugs
act against bacteria. Their spectrum of activity does not include
viruses at all. The use of antibiotics in any viral infection is invariably a
misuse leading to potential harm. Most of the colds, sore throats,
respiratory tract infections, ear infections, and sinus infections are
caused by viruses.29,30 Many kinds of gastroenteritis are also caused by
viruses. These infections by no means respond to antibiotics. Plenty of
fluids, rest, and symptomatic treatment are enough to treat these viral
infections effectively. Antibiotics do not prove of any help in the
following sense:
 They do not kill or limit the growth of viruses and hence do not
cure the infection.
 They do not prevent viral infections or keep people around the
patient safe from contracting the same infection.
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 Antibiotics, however, act on the other bacteria present in the
body, which are otherwise harmless to us or are beneficial like
the bacteria in the gut. This only puts the patient at risk of other
infections.
 Indiscriminate use of antibiotics in infections where they are not
supposed to be used only promotes resistance development
against the otherwise useful antibacterial agents.
It is unfortunate that many health care professionals fail to understand
this and have been making excessive and injudicious use of antibiotics
in viral infections especially in children, making them vulnerable to
severe bacterial infections.
Prevention
Antibiotics, apart from treatment of bacterial agents, are also used in
patients who may not be suffering from any active infection, but are at
risk of acquiring infections due to previous history or a circumstantial
exposure to various pathogens. However, it is necessary to weigh the
benefits and risk of such use of antibiotics where the severity of the
infection should outweigh the potential adverse reaction of the
antibacterial agent. Also, the duration of antibiotic treatment should be
short and its use should be started before the expected risk or as soon
as possible after contact with an infected individual. The most common
use of antibiotics for prophylaxis is following surgical procedures.31,32
Antibiotics may also be given during the procedure and are continually
given after the surgery. The target organism is mostly staphylococcus
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contaminating the surgical suite, the skin of the operating team and
the flora of the patient itself. The antibiotics used during pre-op and
post-op duration are usually cefazolin or clindamycin, cefoxitin, and
fluoroquinolones. Antibiotics, as prophylactic agents, are often used in
nonsurgical cases. Amoxicillin is widely used to prevent cardiac lesions
that are prone to developing bacterial endocarditis and bite wounds.
Rifampin and fluoroquinolones are useful as prophylaxis for people,
who have come in contact with patients of meningococcal meningitis.
In recurrent cystitis, a fluoroquinolone or nitrofurantoin is used and
calls for a long-term treatment for up to 1 year. The use of
antibacterial agents as prophylaxis in children is also common practice
especially, in those susceptible to infections like rheumatic fever and
recurrent otitis media.
The most critical aspect of antibiotic therapy is the right choice of the
antibiotic in a patient with a particular infection. It is a task to choose
from the huge spectrum of options available. Apart from taking into
consideration the above-mentioned parameters, it is also important to
evaluate the cost effectiveness of the therapy being prescribed.
Clinicians must make it a habit to stick to the use of the few drugs
prescribed by experts and professional organizations and must not be
tempted to use new drugs unless their uses are clear. Also, a
knowledge of and desire to upgrade it regularly about the local
susceptibility to pathogens is a must. This will not only help in the
rational use of antibacterial therapy, but will also prevent their misuse
creating more harm than good.
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Broad Spectrum Versus Narrow Spectrum Antibiotics
The selection of an appropriate antibiotic for medical care that will be
effective against a particular microorganism is a crucial task of the
health care provider. If the selection of antibiotic is incorrect, it can
lead to unnecessary adverse effects or the development of resistance,
apart from the patient’s condition worsening. This can further delay
treatment and can lead to progression of the disease by giving more
time to the microorganism to invade the tissues further.33
Traditionally, microorganisms were categorized using the gram staining
method. Based on this, antibiotics are classified by their action against
a spectrum of microorganisms. When the antibiotics can tackle a wider
species of microorganisms the broader is the spectrum of its activity.
Basically, antibiotics solely active against gram positive bacteria, i.e.,
flucoxacillin, are considered narrow in their spectrum of activity, while
antibiotics capable of attacking both gram positive and gram negative
bacteria, i.e., cephradine are broad in their spectrum of activity.34
Historical Perspective
The term ‘broad spectrum antibiotic’ was employed in the middle of
the 1950s, when the microorganism spectrum of activities of
chloramphenicol and the first tetracyclines was strikingly opposed to
the narrow spectrum of activities of penicillin G and streptomycin.
Within the 1960s, aminopenicillins, then ureidopenicillins, became the
broad-spectrum penicillins as compared to penicillin G. Until this
period, the quality of being a broad or narrow spectrum was given to
an antibiotic only when referred to in comparison.
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Later, the reference to a comparator was eliminated, and broad and
narrow lost their relativities and became independent characteristics of
a compound, often used with different meaning and sometimes
improperly. Broad spectrum of antibiotics as an expression of bigger
therapeutic action has mainly been used in pharmaceutical business.
Most antibiotics are prescribed through empirical observation on a
presumptive diagnosis. This suggests that many microorganism
species may be the possible causes of a disease. This kind of
treatment is initiated with the prospect that broad-spectrum antibiotics
can provide coverage for more pathogen. And so, an approach with
broad-spectrum antibiotics is used in a large number of clinical
situations today.35
Because antibiotic medical therapy alters the composition of infected
fluids in the body, investigation samples should be collected prior to
initiation of antibiotic therapy. Since some laboratory testing and
identification can take several days and in some cases, many weeks, if
the infection is severe, the patient is provided broad-spectrum
antibiotic therapy, one that is effective against a wide variety of
different species of microorganisms. It is also accepted that in cases of
mild infections, laboratory identification is not always necessary and a
skilled medical provider can often be able to make an accurate
diagnosis based on patient signs and symptoms.33
After the results of laboratory testing are received and the exact cause
of the illness is identified, the therapy may be switched to a more
narrow spectrum antibiotic, one that is effective against the identified
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organism(s). In general, narrow spectrum antibiotics will produce
lesser adverse effects on normal host flora.
Understanding Spectrum of Antibiotics
Broad-spectrum Antibiotics
Broad-spectrum antibiotics are effective against many or more than
one general class of pathogens. Examples include: Amoxicillin,
Ampicillin, Amoxicillin/clavulanic acid, Carbapenems, including
Imipenem, Meropenem, Ertapenem, Gatifloxacin, Levofloxacin,
Streptomycin, Ciprofloxacin, Tetracycline, Moxifloxacin,
Chloramphenicol, Ticarcillin, etc.
Uses:
Broad-spectrum antibiotics are generally used in the following medical
conditions:

In cases where antibiotic treatment is initiated before the
availability of the investigation based results of antibiotic
sensitivity or before arriving at a confirmed diagnosis.

In cases where there is drug resistance and the patient does not
respond to narrow spectrum antibiotics.

In the case of super-infections, where it is suspected that
multiple species of microorganisms might be involved in causing
the illness, therefore recommending either a broad-spectrum
antibiotic or combination antibiotic therapy.
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
As prophylaxis or preventive treatment after an operation, so as
to prevent infections.
Disadvantages:
As these have the ability to affect a wide species of organisms in the
body, as a side-effect, broad spectrum antibiotics can amend the
body's normal microbial content by attacking indiscriminately both the
pathological and naturally present, healthy, beneficial or harmless
microbes. This kind of destruction of the body's bacterial flora gives an
opportunity to drug resistant microorganisms to grow vigorously inside
the body and can lead to a secondary infection. This side effect is more
likely with the utilization of broad-spectrum antibiotics. An example of
such secondary infection is Clostridium difficile or Candidiasis or thrush
in females.36-38
Narrow-spectrum Antibiotics
This term is used for those antibiotics that have restricted activity and
are effective against only one general category of microorganisms.
Examples include: Polymixins are usually only effective against gramnegative bacteria where as glycopeptides and bacitracin are only
effective against gram-positive bacteria. Aminoglycosides and
sulfonamides are only effective against aerobic organisms, while
nitroimidazoles are generally only effective against anaerobes. Other
examples include clarihtromycin, azithromycin, clindamycin,
eryhtromycin, vancomycin.
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Uses:
1.
Narrow spectrum antibiotics are prescribed for a specific infection
when the exact causative organism is identified.
2.
The advantages of narrow spectrum antibiotics are that they will
not kill too many of the normal microorganisms in the body as
compared to the broad-spectrum antibiotics. So, they are less
likely to cause a superinfection.
Disadvantages:
Narrow spectrum antibiotics can be used only if the causative
organism is identified. If the choice of the drug is not accurate, the
drug may not actually act against the pathogen causing the infection,
and thereby delaying the cure.36,38
Selection and Initiation of Appropriate Antibiotic Therapy
As discussed above, since some investigation results can take more
time and are not available within 24 to 72 hours of the test, the
conservative approach for infectious cases are often broad-spectrum
antibiotics guided by the clinical presentation. It has been seen that
inappropriate selection of therapy for infections in critically ill,
hospitalized patients is usually associated with adverse outcomes,
including higher chances of morbidity and mortality as well as
increased length of hospital stay. Hence, this common approach of
introducing a broad-spectrum antimicrobial agent as initial empiric
therapy with the intent to cover multiple possible microorganisms has
taken root based on the associated specific clinical symptoms seen in
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most cases. This approach is seen in both community and hospital
acquired infections.
Once laboratory results are available and the etiologic microorganism
is identified, a confirmed diagnosis is made. Every attempt should be
made to narrow the antibiotic spectrum. This is a critical element of all
antibiotic medical therapy because it cannot only decrease the expense
of the treatment, but also reduces the toxicity and prevents the
development of antimicrobial resistance in the community.
Antimicrobial agents with a narrower spectrum ought to be directed at
the foremost probable pathogen for the period of therapy for infections
like community acquired pneumonia or cellulitis in the ambulatory
setting because specific laboratory tests are not typically performed.36
Timing of Initiation of Antimicrobial Therapy
The temporal arrangement of initial antibiotic therapy ought to be
guided by the urgency of the case. In patients who are critically ill, like
those in septic shock, bacterial meningitis, febrile neutropenic patients
etc, introduction of broad-spectrum antibiotic therapy should be
initiated as soon as possible, after or concurrently with collection of
diagnostic samples. In more stable clinical cases, this conservative
approach of introduction of empirical therapy can be deliberately
withheld considering the adverse effects on the normal microbial
activity and symptomatic treatment can be provided until all required
samples or specimens are collected and submitted to the microbiology
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laboratory. Examples of such stable clinical circumstances are subacute
bacterial endocarditis and vertebral osteomyelitis.
Patients with above mentioned infections are usually chronically ill for
a period of several days to weeks before presentation, and
administration of antibiotic therapy can be delayed until multiple sets
of blood cultures (in the cases of endocarditis) or disk space aspirate
and/or bone biopsy specimens (in cases of osteomyelitis) have been
obtained. Premature initiation of broad-spectrum antibiotic therapy in
these circumstances can suppress growth of microorganism and
preclude the opportunity to establish a microbiological diagnosis, which
is critical in the management of these patients, who may need
treatment for several weeks or months of a narrow spectrum antibiotic
therapy to achieve complete cure.36
A Comparison of Empiric and Definitive Antimicrobial Therapy
In most cases, antibiotic therapy is best conducted by administering a
single drug. Combining two antibiotics may actually decrease every
drug’s effectiveness, a phenomenon known as antagonism. If incorrect
combinations are prescribed, the usage of such multiple antibiotics
additionally has the potential to promote resistance. Empirical
antibiotic therapy is warranted, if several different organisms are
causing the patient’s infection, or if the infection is so severe that
therapy must be started before laboratory tests have been completed.
Multi drug therapy is clearly warranted in the treatment of tuberculosis
or in patients infected with HIV.33
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As discussed earlier one common adverse effect of broad-spectrum
antibiotic therapy is the appearance of secondary infections, known as
superinfections. This occurs when microorganisms normally present in
the body are destroyed. These helpful and harmless microorganisms or
host flora are present in the skin, upper respiratory, genitourinary
system, and intestinal tract. Some of these organisms serve a useful
purpose by producing antibacterial substances and by competing with
pathogenic organisms for space and nutrients. Removal of host flora
by an antibiotic offers the remaining microorganisms an opportunity to
grow, which leads to overgrowth of pathogenic microorganisms.
Host flora themselves can cause illness if allowed to proliferate without
control, or if they establish colonies in abnormal locations. For
example, Escherichia coli is part of the host flora in the colon, but can
become a serious pathogen if it enters the urinary tract. If the
patient’s immune system becomes suppressed, host flora can also
become pathogenic. Microbes that become pathogenic when the
immune system is suppressed are called opportunistic organisms.
Viruses such as the herpes virus, and fungi are examples of
opportunistic organisms that exist in the human body, but may
become pathogenic if the immune system is suppressed.
Superinfections ought to be suspected if a new infection appears while
the patient is on anti-infection therapy. Signs and symptoms of a
superinfection commonly include diarrhea, painful urination, bladder
pain, or abnormal vaginal discharges. In general, broad-spectrum
antibiotics, as they attack wider species of microorganisms, are more
likely to cause superinfections in the patient.33 The term narrow
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spectrum agent is occasionally considered to be a synonym of targeted
microorganism therapy and an indicator of a medical provider’s
concern for ecology. It has been stated that the diagnosis of an
infection as possible should direct the therapeutic decision to the
foremost appropriate compound. The acceptable treatment of any
disease is that which has been proven to cure patients with similar
disease. There is also a contradictory opinion that an appropriate
antibiotic treatment is never defined by its antibacterial spectrum.35
There are many guidelines where, without adequate clarification or for
unacceptable reasons, it is argued that narrow spectrum antibiotics
should be used. It may be asserted that they are less likely to select
resistant bacteria. This statement is wrong. There are a lot of naturally
resistant species of microorganisms to narrow-spectrum and broadspectrum antibiotics and the fastest choice happens among naturally
resistant species.
It is true that narrow spectrum antibiotics are more microorganism
targeted, but the point to be thought of is whether they are the
appropriate treatment. Furthermore, it can also be argued that the
label of broad or narrow is given arbitrarily; cephalosporins are in fact
narrow spectrum antibiotics with a limited activity against
staphylococci or enterococci, no activity against more anaerobes
(apart from the cephamycins), no activity against intracellular
pathogens, variable activity against non-fermentative organisms. Many
other examples could readily be found to illustrate the misuse of the
two adjectives, broad and narrow, applied to the spectrum of
antibiotics.35
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Classes Of Antibiotics
The chief function of antibiotics is to eliminate infection caused by
bacteria. It can do this either by curtailing the growth of the bacteria
to an extent that it ceases to be a nuisance for the body and the
body’s own defense system can combat them. Alternatively, an
antibiotic can proactively kill the bacteria, which is often faster.
Antibiotics, therefore, can be broadly classified into two types, namelybactericidal and bacteriostatic based on their action on bacteria.
Bacteriostatic
As the name itself suggests, these antibiotics stop the growth of
bacteria, but do not kill them. Once the bacterial growth is restricted,
the host’s immune system takes care of the infestation. The major
drawback is seen in cases of immunocompromised patients, as their
body is not capable enough to eliminate these bacteria themselves.
Hence, these drugs are not so efficacious to treat them.
Bactericidal
These antibiotics directly kill the bacteria.39 Hence, the immunity
status of the patient is immaterial. These drugs actively cause the
death of the bacterial cells in different ways. The only downside in
these types of antibiotics is that they are very toxic to the bacteria;
there are chances of toxicity to the host too.
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Bactericidal Antibiotics
Penicillins
The penicillins are one of the oldest antibiotics40 that is used in the
treatment of bacterial infections caused due to staphylococcus and
streptococcus. It is a part of the beta-lactam family of antibiotics, and
therefore has a similar mode of action, i.e., inhibiting the bacterial cell
growth, which ultimately kills the bacteria. All bacterial cells have a
protective envelope known as a cell wall. This cell wall contains
peptidoglycans as one of the basic components. A peptidoglycan is a
macromolecule with a net-like composition and its function is to
provide rigidity and support to the outer cell wall. A single
peptidoglycan chain has to be cross-linked with other peptidoglycan
chains with the help of the enzyme DD-transpeptidase (also called a
penicillin binding protein — PBP) to form the cell wall. It is seen that in
a complete lifecycle of the bacteria, the cell wall, i.e., the
peptidoglycan crosslinks keep on changing continuously so as to adapt
to the frequent cycles of cell growth and replication.
Penicillins are made up of distinct four-membered beta-lactam rings,
which is similar to the other antibiotics in the beta-lactam family. The
bacteria are killed due to the beta-lactam ring of penicillin binding to
DD-transpeptidase,40 which thereby prevents the bacteria’s crosslinking activity and disrupts new cell wall formation. In the absence of
the cell wall, the bacterial cell is exposed to the external elements like
water and molecular pressures, resulting in death. These cell walls are
seen only in bacteria, not in human cells; the action of penicillin is only
on bacterial cells and not on the human cells.
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When compared, it has been observed that penicillin is more effective
against gram-positive bacteria than gram-negative bacteria as grampositive bacteria have thicker cell walls containing higher levels of
peptidoglycans, whereas gram-negative bacteria have thinner cell
walls with low levels of peptidoglycans. Also, they are surrounded by a
lipopolysaccharide (LPS) layer, which prevents antibiotic entry into the
cell.
Cephalosporins
Cephalosporins also belong to the family of beta-lactam antibiotics and
hence their mode of action is very similar to that of penicillins. They
disturb the synthesis of the peptidoglycan layer that forms the
bacterial cell wall. The peptidoglycan layer plays a vital role in
maintaining cell wall structural integrity.
Transpeptidases known as penicillin-binding proteins (PBPs) are
needed in the last step for the synthesis of the peptidoglycan. The
PBPs bind to the D-Ala-D-Ala chain at the end of muropeptides, which
are the peptidoglycan precursors, to crosslink the peptidoglycan. It is
at this stage that the beta-lactam family antibiotics play the role of
mimicking the D-Ala-D-Ala site, thereby preventing the PBP
crosslinking of peptidoglycan. The first generation cephalosporins have
predominant action against gram-positive bacteria, whereas the later
generations are active against gram-negative bacteria.
Quinolones
Of the family of quinolones, ones that are most commonly used in
medical practice are fluoroquinolones. The first two generations act by
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inhibiting particularly the topoisomerase II ligase domain and leaves
the other two-nuclease domains unharmed. It is due to this alteration
along with the continuous action of the topoisomerase II in the
bacterial cell, that the DNA fragmentation takes place through the
nucleasic activity of the unharmed enzyme domains.
Fluoroquinolones belonging to the third and fourth generation are all
the more specific to the topoisomerase IV ligase domain. Hence, they
cover more gram-positive bacteria. Fluoroquinolones have the
capability of entering the cells easily through porins and are commonly
used in treatment of intracellular pathogens like Legionella
pneumophila and Mycoplasma pneumoniae.41 Fluoroquinolones act on
both gram-positive as well as gram-negative bacteria and hence play
an important role in treating grave bacterial infections, hospital
acquired infections and cases where the host seems to be resistant to
the older antibiotics.
Glycopeptides
Glycopeptide antibiotics are large, rigid molecules that obstruct the
last stage of peptidoglycan synthesis in bacterial cell wall to destroy
bacteria. It is seen that glycopeptides are very specific in binding to
the bacterial cell walls only as the highly specific configurational
peptides required for bonding are found only in bacterial cell walls.
Hence, they are said to be selectively toxic too.
Glycopeptides interact with L-aa-D-aa-D-aa peptides by hydrogen
bonding, thereby forming stable complexes. With the help of this bond,
glycopeptides interrupt the process of formation of the basic glycan
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chains that form the backbone of the cell wall. Due to this interruption,
further transpeptidation reaction is also hampered, which provides
additional strength to the cell wall. It is due to this mechanism of
binding a heavy inhibitor to the outer membrane of the substrate,
which results in unavailability of the active sites for the enzymes to
align precisely. It is very difficult for bacteria to override this process
and develop resistance to glycopeptides in comparison with other
antibiotics.
Because of their toxic effects, glycopeptide antibiotics are not vastly
used. Their usage is limited to patients who are seriously ill, those who
are very sensitive to beta-lactam antibiotics or are infected with
species that are resistant to beta-lactam. These antibiotics are very
effective against gram-positive cocci.
Monobactams
Monobactams are the class of antibiotics that belong to a group of
monocyclic β-lactams. Monobactams are derived from the bacteria
Chromobacterium violaceum. Aztreonam is the only monobactam that
is used in clinical practice currently. It is mainly used in treating
infections caused due to gram-negative aerobic organisms.
The mechanism of action is inhibition of mucopeptide synthesis in the
bacterial cell wall, which in turn blocks peptidoglycan crosslinking. It is
inclined towards penicillin-binding protein-3 as compared to penicillinbinding protein-1a. Aztreonam is not too effective against grampositive and anaerobic bacteria as it does not bind well with their
penicillin-binding proteins. Aztreonam has predominant action against
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gram-negative bacteria and has no much action against anaerobes or
gram-positive bacteria. Aztreonam is a useful alternative for patients
with aerobic gram-negative infections who are allergic to penicillin.42
Carbapenems
Carbapenems also belong to the beta-lactam class of antibiotics. They
are generally used in treating infections that are caused by multidrug
resistant bacteria. They are used in hospitalized patients who are
critically ill.43 These drugs kill the bacteria by preventing the cell wall
synthesis, as they bind to PBPs. They have a broader spectrum of
action as compared to cephalosporins and penicillins. Also, they are
highly effective as they are hardly affected by the general mechanisms
of antibiotic resistance.
Because of their broad-spectrum action, carbapenems are wildly used,
be it for pneumonia, systemic infection, urinary tract infections,
abdominal infections or other bacterial infections.
Bacteriostatic Antibiotics
Tetracyclines
Tetracyclines curb protein synthesis by obstructing the binding of
charged aminoacyl-tRNA to the A site on the ribosome. Tetracyclines
attach themselves to the 30S subunit of microbial ribosomes, thereby
preventing the addition of new amino acids in the developing peptide
chain. This action of tetracyclines is generally inhibitory and can be
reversed once the drug is stopped. Although tetracyclines bind to the
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fine ribosomal subunit of prokaryotes and eukaryotes (30S and 40S,
respectively), the mammalian cells are not much susceptible to the
effects of tetracycline. This happens because the bacteria actively
pumps tetracycline into its own cytoplasm, whereas the mammalian
cell does not do so. We find that tetracyclines have very limited side
effects on the human cells.
Tetracyclines are commonly used in treating urinary tract infection,
respiratory tract infection, and also in cases where the patient is
hypersensitive to beta-lactams and macrolides. Today, it is also
commonly used in treating skin diseases like acne and rosacea.44
Spectinomycin
Spectinomycin is considered to be a bacteriostatic antibiotic because it
acts by binding itself to the 30S subunit of bacterial ribosome, thereby
disrupting the protein synthesis. There has been another form of
resistance that has surfaced in the 16S ribosomal RNA in Pasteurella
multocida.45 This antibiotic is used in the form of injections for
treatment of gonorrhea in patients who are allergic to penicillin.
Sulphonamides
Sulphonamides act as bacteriostatic agents by playing the role of
competitive inhibitors for enzyme dihydropteroate synthetase (DHPS).
Competitive inhibition is a type of enzyme inhibition in which the
inhibitor binds to the active site on enzyme, thereby preventing the
substrate from binding with the enzyme. Dihydropteroate synthetase
is an enzyme that takes part in folate synthesis.
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By hampering the process of folate synthesis, sulfonamides curb the
growth and multiplication of bacteria, rather than killing them. In
human beings this process does not take place as the source of folate
is through diet. Sulphonamides are used in the treatment of allergy,
cough, fungal infection and also as antimalarial agents.
Macrolides
Macrolides act as protein synthesis inhibitors. Their mode of action is
inhibiting bacterial protein biosynthesis. They seem to do this by,
preventing peptidyl transferase from adding the growing peptide
attached to tRNA to the adjoining amino acid, and by inhibiting
ribosomal translation. There can be another mode of action too, which
involve premature dissociation of the peptidyl-tRNA from the
ribosome.46
Macrolides can do this by binding reversibly to the P site on the
subunit 50S of the bacterial ribosome. This mode of action is
considered to be bacteriostatic. Macrolides are loaded on the
leukocytes and are transported easily at the site of infection.47
Macrolides are highly active against gram-positive bacteria as
compared to that of gram-negative bacteria. It is used in cases where
the host is allergic to penicillin.
Chloramphenicol
Chloramphenicol acts as a bacteriostatic agent by disrupting the
process of protein synthesis. It averts the protein chain elongation by
preventing the peptidyl transferase activity of the bacterial ribosome.
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It binds specifically to A2451 and A2452 residues48 present in the 23S
rRNA of the 50S ribosomal subunit, thereby preventing the formation
of a peptide bond.
Although chloramphenicol and the macrolide both interact with
ribosomes, chloramphenicol is not a macrolide. This is because it
directly meddles with substrate binding, whereas macrolides strictly
obstruct the progression of the growing peptide.49,50,51
Chloramphenicol is used in the treatment of various diseases like
typhoid, cholera, meningitis and also brain abscesses.
Trimethoprim
Trimethoprim acts as a bacteriostatic antibiotic by inhibiting bacterial
DNA synthesis. By binding up with dihydrofolate reductase,
trimethoprim prevents the reduction of dihydrofolic acid (DHF) to
tetrahydrofolic acid (THF). THF is an important precursor in the
thymidine synthesis pathway and therefore any hindrance in this
pathway block bacterial DNA synthesis. It has more than a thousand
fold greater affinity to bacterial dihydrofolate reductase as compared
to that for human dihydrofolate reductase. Another bacteriostatic
antibiotic that is commonly used along with trimethoprim is
sulfamethoxazole.
The mode of action of this antibiotic is by inhibiting dihydropteroate
synthetase, an enzyme that participates further upstream in the same
pathway. Both these drugs are generally are commonly used together
because of their synergistic effects and decreased chances of
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developing resistance. Trimethoprim is a drug of choice in urinary tract
infections, middle ear infections and also traveler’s diarrhea. In
combination with dapsone or sulfamethoxazole, it is used in
pneumocystis pneumonia affecting people suffering from AIDS.52
Modes Of Administration Of Antibiotics
Before an experimental drug or the research drug receives final
approval by the FDA, the pharmaceutical company must provide
detailed information regarding what routes of administration have
been found to be safe and effective for that drug in the research
conducted. Different forms of a particular drug have different actions
when administered by different routes. Some drugs are completely
ineffective when administered by other routes apart from the indicated
route; while some drugs may cause serious adverse events to the
patient if administered by the wrong route.53
There are multiple routes by which drugs can be administered. Some
drugs are approved for use through more than one route and are
manufactured in different forms used for different routes. Each
indicated route of administration of the drug will have distinct
advantages and disadvantages. A drug given by the approved route of
administration will be therapeutic; however, if given by unapproved
routes may be ineffective, harmful to the health, or even fatal.53
Different Routes or Modes of Administration of Antibiotics
A broader way of classifying routes of administration is enteral and
parenteral. Enteral pertains to the gastrointestinal tract, which includes
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oral, buccal, nasogastric route, gastrostomy and rectal routes.
Parenteral pertains to injectables such as intravenous, intramuscular
and subcutaneous routes; and could also include topical and olfactory
routes.54
Clinicians have generally believed that the best way to establish a
good bioavailability of the drug is by administering the drug
intravenously. However, this approach requires establishing indwelling
intravenous access, usually in a hospital setting. For patients who do
not require hospitalization or inpatient treatment, other routes of
antibiotic administration are usually preferred. For example, oral
administration of drugs like penicillin, erythromycin, tetracyclines,
sulfonamides, and chloramphenicol have shown to provide adequate
blood levels and good clinical outcomes with selected infections from
the beginning of the antibiotic era.55 The commonly prescribed route
for administering antibiotics are considered below.53,54,56

Oral: This is the most common route.

Sublingual: Sublingual administration involves placing the drug
(often in a tablet form) under the tongue and allowing it to
disintegrate slowly. Here the tablet is not swallowed, and the
dissolved drug is absorbed quickly through the oral mucosa into the
blood vessels under the tongue and oral cavity.

Rectal: This route is prescribed in certain clinical conditions like
when the patient is vomiting or is unconscious or the drug cannot
be given by injection. Systemic absorption of a drug, if
administered through the rectal route, is slow and unpredictable, so
this route is not used often. However, in certain clinical conditions
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this is the preferred route, such as enema for constipation or Anusol
cream or suppositories for hemorrhoids.

Vaginal: Vaginal route is commonly used to treat certain vaginal
infections by means of ointments or suppositories, i.e., Monistat
vaginal cream or suppositories for yeast infection.

Nasal route and Inhalations: Nasal route of administration usually
involves spraying a drug into the nasal cavity, i.e., Nasonex, a
topical corticosteroid drug is sprayed intransally to treat allergy
symptoms of nasal stuffiness. Some nasal spray drugs can act
systemically throughout the body, i.e., Miacalcin nasal spray for
Paget’s disease of the bones. In olfactory route, the prescribed drug
is inhaled in powdered form or gas or liquid. The drug is absorbed
through the alveoli of the lungs (i.e., an anesthetic gas).

Topical or Transdermal: This refers to all local applications; i.e., the
drug is directly applied to the skin, eyes, hair, and ears.

Intravenous: As the name suggests, this involves injection of the
drug inside the vein.

Subcutaneous: This route of administration involves using a syringe
to inject a liquid drug into the subcutaneous tissue, which is the
fatty layer of tissue just beneath the dermis of the skin, but above
the muscle layer. Since there are only a few blood vessels in this
fatty layer, the drugs are absorbed slower into the system as
compared to intramuscular route.

Intramuscular (IM): It involves the injection of a liquid drug into
muscle mass like the belly or thighs or biceps (area of greatest
mass). As the muscular system is well supplied with blood vessels,
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the drug injected through IM is absorbed more quickly than with
subcutaneous administrations.
Other routes of administration include intra arterial in chemotherapy to
increase drug concentrations at the tumor site, intrathecal directly into
the cerebrospinal fluid, intrasynovial,54 central venous line,
endotracheal tube implantable port, intra articular route, intracardiac
route, intraperitoneal route, intravesical route and umbilical artery or
vein.53 The following section will review the oral, topical and
intravenous routes.
Oral Administration or Per Oral (PO)
The drug is ingested through the mouth, reaching the gastrointestinal
tract.57 Oral route of administration is the most common method of
administration of antibiotics and drugs in general. Through enteral
route (gastrointestinal), the drug eventually reaches the bloodstream.
Oral medications are prepared in various forms:

Solids: tablets, capsules, etc.

Liquids: syrups, etc.
Tablets
Tablets are a solid form of oral antibiotic preparation that is prepared
by compression of the powdered drug and molding it into various
shapes and sizes. They are prepared by mixing active ingredients with
lactose or other sugars, binding agents, or other inert materials, to aid
manufacturing and ascertain drug stability. Many tablets bear
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markings from where they can be broken to ensure correct dosage.
The tablets that do not bear these marks should not be broken.
The compounds used in tablets should be stable in the gastric
environment to avoid degradation. The flavor of a tablet is very
important, as it has to be consumed orally. Tablets with a disagreeable
taste are not easily tolerated, leading to poor patient compliance.
Coating of Tablets:
The surface of the tablet is coated. Commonly used coatings are
enteric, film and sugar coatings. Advantages of coating the tablets are:
 To protect acid labile drugs from dissolving in an acidic
environment of the stomach. The tablet then gets dissolved in
a neutral or alkaline pH; for example, enteric coated tablets.
 To ensure sustained release of the drug so that it gets released
slowly; for example, enteric-coated tablets.
 To prevent local adverse effects; for example, enteric coated
tablets.
 To improve the flavor, for example, enteric-coated tablets, film
coated tablets and sugar coated tablets.
Capsules
Capsules are another solid form of oral antibiotic preparation, in which
the drug is usually encased within a shell of hard or soft gelatin. The
bad taste of active ingredient does not become a hindrance for patient
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compliance. Gelatin capsules are easier to swallow.
Capsules cannot be divided like tablets and need to be consumed
whole. They usually contain a powdered antibiotic, but some capsules
contain drugs in form of paste, semi- liquid or liquid. They are
designed to release the drug in a controlled manner.
Syrups
Syrups are liquid formulations. They are concentrated solutions of
sugar in water. Generally, syrups are resistant to mold, yeasts and
other microorganisms and thus have a fairly good shelf life. They can
be easily administered to children because they are easy to swallow
and the taste can be adapted to suit their palate.
Emulsions and Suspension
Liquid preparations made out of two chemically incompatible
substances are called emulsions or suspensions. Emulsions are the
combinations of two liquids that do not mix well are called emulsions.
Here, one liquid does not distribute uniformly through the other,
separating out as a layer on top. These need to be shaken well before
use and immediately consumed. An emulsifying agent is added to
stabilize the mixture. Additives adversely affect the stability of
mixtures; hence, they need to be avoided.
Suspensions are a finely divided solid dispersed in a liquid gives a
suspension. The stability of this mixture depends on the ability of the
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liquid to wet the solid particles. The advantages are:

Convenient to the patient, very easy to take.

Safe

Painless hence has good patient compliance.

Cheap

Varieties of forms are available.
The disadvantages are:54

Inefficiency due to low-solubility and poor bioavailability.

First pass effect: metabolism of drug in the liver before it
reaches the target organ.

Food and gastrointestinal motility: In the presence of food,
absorption of certain antibiotics is slower, i.e., penicillin, while
some get absorbed faster.58

Local effect: antibiotics affect the normal intestinal flora and
fungal overgrowth may occur. Hence, an antifungal is often
added to the prescription.

Unconscious or comatose patients: administration becomes
difficult and other means of enteral administration are employed,
i.e., administration through gastrostomy or nasogastric tube.
Topical and Transdermal
Topical route refers to all local applications, where a drug is applied
directly to the skin, nails, hair, eyes or ears. The therapeutic effect of
the drug will only extend to the local area.59
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Examples include antibiotic ointments for a skin injury, antibiotic drops
for an ear infection and mydriatic eye drops for glaucoma. Other
examples include all antiseptic creams and ointments, sunscreens,
callous removal products.
Absorption After Topical Administration
Following a topical administration, the drug form does not need to
undergo disintegration; it quickly dissolves in the tissue fluids of the
skin. However, topical drugs do not complete the final step of
absorption and do not go into the blood and their therapeutic effect is
only exerted locally at the site of administration.
Transdermal route of administration is different as compared to the
topical route. Here, the drug is applied directly onto the skin and the
effect of the medicine is felt systemically and not just at the site of the
application. They are manufactured usually in the form of a
transdermal patch, which can be worn on the skin.
The drug is released slowly over one or more days, providing a
sustained therapeutic blood level. Examples include nicotine patches to
quit smoking.
Absorption After Transdermal Administration
In a transdermal patch or transdermal applications, the drug in the
patch reservoir begins to release. Because the drug is in a liquid form,
it does not undergo disintegration, but it dissolves quickly in the tissue
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fluids of the skin and passes through the walls of nearby capillaries,
and is absorbed into the blood.54,55
Intravenous (IV)
Drugs are given into a peripheral vein or by infusion. A bag of
intravenous fluid is hung from an IV pole, which is kept elevated above
the patient. Due to the gravitational effect, the fluid moves through
the IV tubing and into the patient’s vein, drip-by-drip through the
needle. As an alternative, an IV pump can be used to accurately
regulate the dose when extremely small quantities of the drug need to
be pumped into the bloodstream.54,55
Intravenous administration is usually carried out in one of three ways
listed below:53

Bolus: The whole amount of a liquid drug can be injected in a
short period of time through a port in the IV tubing by using a
syringe, which is referred to as an I.V. push.

IV Infusion: The liquid drug can be injected into the fluid of the
IV bag and it is administered to the patient over several hours
also known as IV drip.

IV Piggyback: The drug is first injected into a small IV bag of
fluid that is then further attached (or piggybacked) onto an
existing primary IV line
Examples include Thiopental for induction of general anesthesia,
diazepam for control epileptic seizures, chemotherapy drugs, etc.
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Rapid injections are used in cases of epileptic seizures, cardiac
arrhythmias or acute asthma.
Advantages include:54

Rapid: Response is quick. Plasma concentration can be
monitored and precisely controlled using intravenous infusion.

Total dose: The whole dose of the drug is delivered into the
blood stream directly and the bioavailability is nearly 100%.

Larger doses may be given by I.V infusion over an extended time
and drugs that are poorly soluble may be given in a larger
volume over a period of time.
Disadvantages include:54

Venous access: To find a suitable vein is a difficult task and
requires good clinical skills. It can even cause some tissue
damage at the site of injection.

Toxicity: As the response is rapid, toxicity can be a problem with
fast drug administrations. In such cases, the dose should be
given as an infusion, constantly monitoring for toxicity.

Expensive: Sterile conditions, pyrogen testing and higher volume
of liquid drug mean the greater the cost of preparation, transport
and storage.
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Side Effects of Antibiotics
Any drug that has an effect can have a side effect. In the course of
treatment with antibiotics, the patient may experience other unwanted
symptoms, along with the desired therapeutic effect of these
medicines. When taken under proper guidance, antibiotics are very
safe drugs, but like any other drug, antibiotics also have their own side
effects. Sometimes the side effects can be severe enough to hamper
the patient from completing the entire course of medication.
Antibiotics can have mild to severe side effects depending from patient
to patient. This also varies from antibiotic to antibiotic. There are
various side effects that are commonly seen irrespective of the type of
antibiotic the person is taking. Following are a few of the adverse
effects caused by antibiotics.
Antibiotic-associated Diarrhea
The patient suffers from diarrhea just because he/she is taking
antibiotics. There is no other explanation for this diarrhea. Studies
suggest that around five to twenty five percent of patients can suffer
from antibiotic-associated diarrhea. The cause of diarrhea is the effect
of antibiotics on the normal gut flora; these helpful bacteria get
eradicated when the patient consumes an antibiotic. Therefore, there
is increased production of infectious bacteria like Clostridium difficile.
Generally, the diarrhea is not that bothersome and resolves
spontaneously once the drug is stopped, but if the diarrhea is severe,
contains blood or is associated with abdominal cramps or vomiting,
then it is necessary to be stopped. Antibiotics like amoxicillinclavulanate, ampicillin, and cefixime generally cause antibiotic-
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associated diarrhea; also other antibiotics like cephalosporins,
fluoroquinolones, azithromycin, clarithromycin, erythromycin, and
tetracycline can cause diarrhea.60
Vaginal Yeast Infections or Oral Thrush (Candida Species)
Antibiotics can also affect the normal flora present in the vagina. When
the vaginal flora is affected, it leads to increased growth of fungi.
Candida albicans is the commonest fungal infection that affects the
vagina, as even in healthy condition, it is present in the vagina in
small quantities. Under normal circumstances, candida is present even
in the oral cavity, gastrointestinal tract, and on the skin, but does not
produce any signs and symptoms of infection. When a person is on
antibiotics, the bacterial colonies are on target and the fungal colonies
do not have much competition from bacteria and start overgrowing,
leading to an active infection producing symptoms of a fungal
infection.
Stevens Johnson Syndrome (SJS) and
Toxic Epidermal Necrolysis (TEN)
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
are rarely seen, but are serious allergic reactions to substances. They
are generally seen with ingestion of antibiotics that cause severe skin
and mucous membrane disorders. The antibiotics that can cause SJS
and TEN are sulfonamides, penicillins, cephalosporins, and
fluoroquinolones. Both SJS and TEN can produce symptoms of rash,
peeling of skin, sores on the mucous membranes and also both can be
life-threatening.
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Injection Site Reactions and Phlebitis
When an antibiotic is given intravenously, a local inflammatory
reaction to the antibiotic can occur at the injection site or inflammation
of the vein (phlebitis). If the reaction takes place, the vein and the site
of the access becomes red, swollen and tender. Under ideal conditions,
the needle should be removed and new access should be taken, so
that the reaction at the site of injection settles.
Toxicity
Almost all antibiotics produce systemic toxicity to a certain extent. This
is predictable and mentioned along with the antibiotic. Some
antibiotics are extremely safe and may be given up to a hundred-fold
range without apparent toxicity. Examples include erythromycin,
penicillin, cephalosporins. Some others have a very low therapeutic
index and need to be monitored for apparent side effects. Commonly
affected organs are the liver, kidneys, and bone marrow. Examples
include aminoglycosides cause 8th cranial nerve toxicity while
chloramphenicol produces bone marrow depression. Still others like
vancomycin can produce hearing loss and kidney damage as the
therapeutic range of dosage is extremely low.
Drug Resistance
A major problem that has emerged due to injudicious and overuse of
antibiotics is resistant bacteria. Bacteria develop a natural resistance
to antibiotics when overused and the next generations of bacteria that
are produced are resistant to these antibiotics. This has lead to the
birth of superbugs like multidrug resistant tuberculosis, methycillin
resistant streptococci, etc.
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Superbugs are resistant to existing antibiotics, making them extremely
difficult to treat and cure, and they also lead to a tremendous amount
of morbidity and mortality. The hospital-acquired infections of resistant
clostridium difficile are glaring examples of antibiotic resistance.
Nutritional Deficiencies
Prolonged use of antibiotics leads to washing off of the helpful gut flora
that produces vitamin B12 and K. Antibiotics like neomycin can lead to
steatorrhea and malabsorption.
Hypersensitivity Reactions
All antibiotics are capable of producing a hypersensitivity reaction.
These are absolutely unpredictable and can happen to anyone. These
hypersensitivity reactions are often unrelated to the dose. Reactions
ranging from a mild rash to itching to severe anaphylactic shock can
be seen. Common antibiotics that are known to produce such reactions
are sulfonamides, penicillin, fluoroquinolones and cephalosporins.
There is no way to predict these reactions and the only way is to keep
patients well educated that these reactions can occur to anyone and
that a health care provider must be approached the minute any of
these symptoms occur.
Superinfections
Excessive antibiotics often lead to the emergence of an altogether new
infection as a result of the therapy. This is because the antibiotics alter
the gut flora. The natural flora produce substances called bacteriocins
that inhibit pathogenic organisms. Once these helpful flora are
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destroyed, washed away or altered, the competition for nutrition also
reduces. This paves the way for opportunistic pathogens to flourish,
i.e., candida albicans, resistant staphylococci, pseudomonas, proteus,
etc. Commonly associated antibiotics that produce such
superinfections are chloramphenicol, tetracyclines, ampicillin, and
newer generation cephalosporins.
When the host is immunocompromised, these infections occur at an
even higher rate with greater severity. Conditions like steroid therapy,
agranulocytosis, malignancies like leukemia, diabetes, DLE and AIDS
predispose patients to superinfections and one must be extremely
careful while prescribing antibiotics in such patients. Each class of
antibiotics produces a certain set of reactions that are common to the
antibiotics of that group, even though most reactions are common to
all antibiotics. Following are the adverse reactions caused by specific
antibiotics belonging to different classes.
Penicillins:
Other antibiotics in this class include penicillin, amoxicillin, amoxicillinclavulanate, ampicillin, piperacillin-tazobactam, nafcillin, oxacillin.
Apart from the common side effects mentioned above, penicillin can
cause urticaria, seizures, angioedema, neurotoxicity and
pseudomembranous colitis. Severe allergic reaction can occur in
0.03% of patients.61 It is also seen that the patients who receive
antibiotics from the beta- lactam group have a 1% chance of
developing allergic reactions.62
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Amoxicillin can cause severe reactions like hives, jaundice, unusual
bleeding seizure, difficulty in breathing, severe bloody diarrhea, and
chest pain. Adverse side effects of ampicillin include anaphylaxis, low
platelet and RBC count, erythema multiforme, and sometimes it may
even cause pseudomembranous colitis.
Cephalosporins:
Other antibiotics in this class include cephalexin, cefaclor, cefuroxime,
ceftibuten, cefdinir, cefixime, ceftriaxone.
In general, side effects of cephalosporins do not cause many side
effects. Hypersensitivity reactions are not very common, as are seen in
cases of penicillin. Side effects that can be seen due to cephalosporins
are fever, arthralgia and exanthema, which were seen in children when
given cefaclor. Modern cephalosporins generally do not cause
nephrotoxicity, but the reduction in renal function has been observed
in cases where high doses of ceftazidime were administered.
Cephalosporins like ceftriaxone and cefoperazone, are excreted
through the kidneys and also the bile; hence there is increased risk of
diarrhea that can be due to cytotoxin-producing strains of Clostridium
difficile. Eosinophilia and thrombocytosis are seen however are mostly
not caused due to any adverse reactions but to signs of healing of the
infections treated.63
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Aminoglycosides:
Other antibiotics in this class include gentamicin, tobramycin,
amikacin.
Adverse effects caused due to aminoglycosides are mainly seen in
kidney and ear.64 Experimental data suggest that gentamicin is more
toxic than tobramycin and amikacin.65 Aminoglycosides cause acute
kidney injury, thereby causing a significant rise in serum creatinine
levels.66 Using aminoglycosides on a regular basis can cause subclinical
damage to the kidneys, thereby leading to chronic kidney disease.
Patients receiving high doses of aminoglycosides, continuously suffer
from ototoxicity67 as well as vestibulotoxicity. It can even cause
dizziness and nystagmus.
Carbapenems:
Other antibiotics in this class include meropenem, ertapenem,
doripenem, imipenem-cilastatin.
Serious and sometimes fatal allergic reactions may be seen in patients
being treated with carbapenems.68 Seizures can occur in people taking
imipenem and meropenem in limited doses.69 People being treated
with carbapenems can even suffer from diarrhea caused due to
clostridium difficile.70
Glycopeptides:
Other antibiotics in this class include vancomycin and telavancin.
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Vancomycin can lead to ‘Red man syndrome’ whose symptoms are
flushing or erythematous rash affecting the face, neck and upper
torso, itching and hypotension. Other side effects that are seen due to
vancomycin are nephrotoxicity including renal failure and interstitial
nephritis, blood disorders including neutropenia. It can also lead to
deafness, that is reversed once the drug is stopped. Telavancin causes
alteration of taste, nausea, vomiting, headache and dizziness.
Macrolides:
Other antibiotics in this class include erythromycin, azithromycin,
clarithromycin and roxithromycin.
Side effects:
There are 15% to 20% of people taking erythromycins that experience
gastrointestinal symptoms. Except for troleandomycin and some
erythromycins administered in big doses and for prolonged periods,
the hepatotoxic potential of macrolides, that rarely or never form
nitrosoalkanes, is not much for josamycin, midecamycin, miocamycin,
flurithromycin, clarithromycin and roxithromycin. It is negligible or
absent for spiramycin, rikamycin, dirithromycin and azithromycin.71
Sulfonamides:
Other antibiotics in this class include trimethoprin-sulfamethoxazole,
erythromycin-sulfisoxazole, and sulfadiazine.
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Sulfonamides can cause many side effects like urinary tract disorders,
hematopoietic disorders, porphyria, and hypersensitivity reactions.
They even cause strong allergic reactions when given in high doses.
The most common manifestation of a hypersensitivity reaction to sulfa
drugs is rash and hives. There are other life-threatening reactions to
sulfa drugs like Stevens–Johnson syndrome, toxic epidermal
necrolysis, agranulocytosis, hemolytic anemia, thrombocytopenia,
fulminant hepatic necrosis, and acute pancreatitis.
Tetracyclines:
Other antibiotics in this class include tetracycline, doxycycline, and
minocycline.
Tetracyclines commonly do not produce many side effects. There is,
however, an increased risk of developing phototoxicity. Also, there is
increased risk of sunburns when exposed to light from the sun or other
sources. It can even cause stomach or bowel upsets, and rarely some
allergic reactions.
On rare occasions, patients complain of severe headache and vision
problems that may be signs of dangerous secondary intracranial
hypertension. Tetracyclines are teratogens and can cause teeth
discoloration in the fetus as they develop in infancy. Sometimes even
adults complain of teeth discoloration (mild gray hue) after taking
tetracyclines. Some patients on tetracyclines need medical supervision
as it can lead to steatosis and liver toxicity.72,73,74
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Quinolones:
Other antibiotics in this class include ciprofloxacin, levofloxacin,
moxifloxacin, and ofloxacin
Fluoroquinolones are considered to be very safe antibiotics and do not
cause any serious or life-threatening adverse reactions. Commonly
observed side effects are gastrointestinal reactions (nausea,
dyspepsia, vomiting) and CNS reactions such as dizziness, insomnia
and headache. Of the potentially serious side effects, phototoxicity has
been reported with varying frequencies with the different
fluoroquinolones.75
Lincosamides:
Other antibiotics in this class include lindamycin and lincomycin
Lincosamides affects the gastrointestinal tract, thereby causing
symptoms of stomach pain, diarrhea, nausea, vomiting, and
pseudomembranous colitis. It can cause allergic reactions like skin
rash and itching. Hematological reactions include neutropenia,
thrombocytopenia and sometimes jaundice.
Antituberculosis agents:
Antibiotics in this class include rifampin, rifabutin, isoniazid,
pyrazinamide, ethambutol, and dapsone.
Isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin are
the five first-line antituberculosis medications. Hepatotoxicity to
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isoniazid is a serious problem. Side effects of these antituberculosis
drugs are common, and include hepatitis, cutaneous reactions,
gastrointestinal intolerance, hematological reactions and renal failure.
It is better that these adverse effects are recognized earliest so that
the associated morbidity and mortality is reduced.76
Metronidazole is another antibiotic that is commonly used to treat
bacterial infections of the vagina, stomach, skin, joints, and
respiratory tract. It can cause nausea, vomiting, headache, dizziness,
vaginal candidiasis, and metallic taste in mouth. It can cause
numerous adverse reactions, such as, numbness or tingling in the
hands or feet, white patches or sores inside the mouth or on lips,
painful micturation or sensation of burning while passing urine,
diarrhea that is watery or bloody, vision problems, pain behind the
eyes, trouble concentrating, slurred speech, mood or behavior
changes, tremors, muscle twitching, seizure (convulsions), fever,
chills, muscle pain, confusion, sore throat, neck stiffness, increased
sensitivity to light, drowsiness, etc.
Intake of alcohol should be avoided while the patient is on this
medication, including for 3 days after completing the course of
medication as it may lead to cramps, redness of skin and can discolor
the urine to red-brown.
Whenever the patient is experiencing any worrisome or serious side
effect of an antibiotic, it is advisable that the antibiotic be changed,
the dose adjusted or even discontinued altogether. Allergic reactions
to antibiotics are one of the most common reasons that people may be
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admitted to the emergency room.77 Mild allergic reactions can be
easily taken care of but severe allergic reactions like anaphylactic
shock that results in difficulty to breathe is a life threatening condition
and requires immediate medical attention. Clearly, antibiotic therapy is
like a double-edged sword that is extremely beneficial when used
wisely, but can lead to extremely devastating and fatal outcomes if
overused or misused.
Interactions Of Antibiotics
The discovery of antibiotics completely changed the face of healthcare
and heralded a completely new era in medical practice. Antibiotics now
are commonplace in general medical practice for a number of
infectious diseases. Since antibiotics are regularly prescribed, there is
always a strong potential for drug interactions of antibiotics with other
drugs, leading to unexpected adverse effects and even life threatening
alterations. The degree of interaction depends upon the dosage of
antibiotic prescribed. There are a number of classes of antibiotic drugs
and it is important to know the interactions of these antibiotics with
other drugs administered. Most interactions of antibiotics occur at the
absorption stage.
Antibiotics and Oral Contraceptive Drugs
There has always been a lot of controversy on the interaction of
antibiotic with oral contraceptives (OCP) leading to failure of birth
control and resulting in unwanted pregnancy. Though the chances
appear to be low, the actual incidences of women getting pregnant
while on antibiotics as well as oral pills are still unknown.
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Most women currently taking oral contraceptives are advised to opt for
another form of birth control such as a condom until the entire course
of antibiotic treatment is completed. The frequency78 and occurrence
of unwanted pregnancies is not well recorded and very few cases seem
to be documented on the occurrence of these interactions. Since so
many women are taking oral birth control pills, it is unsure whether
the failure of the pill was due to antibiotic use or the expected failure
of oral contraceptive medication.
Most antibiotics do not affect oral contraceptives,79 only certain classes
of these drugs. Antibiotics that increase the rate of metabolism of the
pills include rifampin and griseofulvin, which are the most likely ones
to interact. Other classes of antibiotics such as penicillins and
tetracyclines also carry a risk, but much lower than the above ones.
Normal Metabolism of OCPs in the Body
Birth control pills contain estrogens and progestins in varying
amounts. The estrogenic part of the pill is ethinyl estradiol in most oral
contraceptive pills. The normal pathway of metabolism of this drug in
the body is through the liver by cytochrome P450 3A4. It is then
excreted in the bile and broken down by the flora in the gut and
reabsorbed as an active component, which prevents conception.
Mechanism of Antibiotic and Oral Pill Interaction
There are two proposed mechanisms80 by which these antibiotics are
thought to interact with birth control pills. These two potential ways by
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which antibiotic interaction can occur with oral contraceptive pills is
either in the liver during metabolism or in the enterohepatic circulation
through the intestinal flora.
The enzymes in the liver metabolize most of the medications
prescribed including the hormones in these pills. Certain antibiotics are
also metabolized by the same enzymes, which act on the hormones
thereby enabling the hormones in the oral contraceptive pills to be
rapidly metabolized. As a result, the levels of the hormones reduce in
the blood circulation causing a reduction in the effectiveness of these
pills. Rifampin81 is a potent inducer of cytochrome P4503A4 and
hastens the elimination of estrogen component as well as
progesterone. Rifampin also has a strong affinity for sex hormonebinding globulin, which usually binds to progesterone. Drugs that have
high affinity for SHBG reduce the levels of progestin. This happens
because rifampin affects the binding capacity.
Another mechanism by which antibiotics can interact with oral
contraceptive pills is by affecting the breakdown of estrogen
components of active free estrogen, which can be absorbed again
through the enterohepatic circulation. This is another possible pathway
for antibiotics to interact with these drugs and reduce the levels of
good bacteria present in the gut flora. These bacteria are required for
the breakdown of estrogens in the oral pills to release the active
compounds of these hormones. There are a number of factors that can
influence these interactions, which include:82

Amount of estrogen and progesterone in the oral contraceptive
pill
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
Dose and duration of antibiotic prescribed

Fertility of couple

Individual reaction of bacterial flora to drugs which can vary
Thus, the risk of getting pregnant while on antibiotics and oral
contraceptives is very small, yet there still is a small chance of
pregnancy occurring. It is also very difficult to predict which women
are at a higher risk. Currently, with newer variants of contraceptive
pills, which have lower doses of hormone in them to reduce the side
effects, certain women may be at a higher risk of getting pregnant if
they start a course of antibiotics. These include low dose oral
contraceptive pills, which can be affected by antibiotics.
Any woman who starts a course of antibiotics should be counseled of
the chances of birth control failure due to drug interactions. Though we
have identified that the chances are very low, it is always advisable to
be cautious when using certain antibiotics with oral birth control pills
together. For any woman taking antibiotics, especially rifampin or
griseofulvin, especially long-term, the provider should provide advise
for the woman to switch either to a non-hormonal method of birth
control such as condoms or use a higher dose of oral contraceptive
pills. For a short-term course of antibiotics, it would be advisable to
continue the pills along with a backup, such as condoms or abstinence
from intercourse, until the course of drugs is over.
Apart from counseling, it is important to let women know that it is
impossible to know the chances of who is at a higher risk of pill failure.
Any episode of bleeding while on antibiotics and oral contraceptive
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pills, or previous history of oral contraception failure, should lead to
the use of a non-hormonal method of contraception.
In spite of numerous studies and clinical trials, the association
between antibiotics and oral pills still remains very controversial. Oral
pills have a normal failure rate83 of 1% in normal conditions and about
8% in typical use. Thus, it still remains not clearly understood whether
birth control failure occurs due to antibiotic interaction or the inherent
failure rate of the pill.
Antibiotics and Alcohol
The most popular question that is usually asked to practitioners by
patients is whether they can consume alcohol when prescribed a
course of antibiotics. Since antibiotics and alcohol can cause similar
side effects such as nausea, abdominal pain as well as drowsiness,
when they are taken together they can produce an increase in side
effects.
Most antibiotic boxes today have a warning that patients should avoid
consumption of alcohol while on the drug. Quite a number of
individuals are unaware that alcohol can interact with many drugs and
can cause a number of adverse effects. In fact, a significant proportion
of hospital admissions because of adverse drug reactions are
attributed to alcohol. However, the exact interaction of antibiotics with
alcohol84 is still not clearly understood and only a few antibiotics seem
to have an interaction with alcohol.
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Moderate consumption of alcohol seems to have no effect when taken
along with antibiotics. A growing concern arose due to the fact that
chronic alcoholics tend to have a weaker immune system due to the
effect of alcohol on immune cells predisposing them to more number
of infections. Drinking large amounts of alcohol not only reduces a
person’s immunity, but also dehydrates the body, which prevents the
body from recovering at a normal pace. With the increased prevalence
of alcohol consumption85 the healthcare community should be
enlightened about the possible drug alcohol interactions in order to
educate patients.
Normal Metabolism of Alcohol
It is vital to understand the exact metabolism of alcohol in the body to
be blue to understand the interactions of alcohol with antibiotics.
About ten percent of the consumed alcohol undergoes metabolism in
the stomach, intestine and liver. Alcohol is metabolized to aldehyde by
an enzyme ADH (aldehyde dehydrogenase). Aldehyde is a toxic
compound that is metabolized by aldehyde dehydrogenase ALDH to
acetate; following this, alcohol is transported to various tissues of the
body to show its effect. It is later transported to the liver for
metabolism and elimination.
Alcohol is broken down in the liver by the enzyme P450. This enzyme
also metabolizes various other drugs. Thus, alcohol can alter the
dynamics of medication, which includes their absorption and
metabolism.
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Interactions with Certain Antibiotics
One of the most common interactions of alcohol occurs with
metronidazole, which is commonly given for a number of infections of
skin, joints, respiratory tract and gastrointestinal tract. Taking these
drugs along with alcohol can cause a disulfiram-like reaction, which
includes nausea, cramping, vomiting, rapid heart rate as well as
difficulty in breathing. This disulfiram-like reaction can occur with
other antibiotics, such as to tinidazole and cefotetan,86 as well as
third-generation medication like cephalosporin, ceftriaxone, etc., which
is extremely rare. This reaction occurs due to inhibition of ADH, which
stops the oxidation of acetaldehyde irreversibly. Thus, these
symptoms occur due to elevated levels of acetaldehyde.
Patients must be advised to avoid alcohol for at least 24 hours after a
course of metronidazole and 72 hours after a course of tinidazole.
Some antibiotics can also cause certain central nervous system side
effects such as sedation, drowsiness, confusion or dizziness. Alcohol
causes these same side effects as well. If alcohol is combined with
these antibiotics, an additive effect takes place. This interaction can be
quite serious and dangerous, especially if the patient has to drive, is
elderly or taking other depressant medications.
Isoniazid,87 which is a part of anti tuberculosis treatment, is also
known to have some interaction with alcohol. In chronic alcoholics, this
drug is quickly metabolized which can lead to a reduction in circulating
levels of drug and thereby reduce its effectiveness. Along with this, a
combination of alcohol and isoniazid also seems to show a disulfiram-
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like reaction and cause some level of hepatotoxicity. Liver toxicity
occurs due to high levels of drug still present in blood circulation due
to lack of enzyme to metabolize it.
Linezolid is not a very regularly used antibiotic, and it interacts with
alcohol in a different way. Certain alcoholic drinks88 contain a
substance called tyramine, which interacts with linezolid and leads to
acceleration of blood pressure.
Doxycycline is a commonly prescribed antibiotic, usually given for
acne. In individuals with a chronic history of alcohol consumption,
there seems to be some level of interaction between the drug and
alcohol that lowers the drugs efficacy.
Consuming alcohol while on antibiotics can also affect the rate of
recovery. Adequate rest, diet and sleep are needed for a speedy and
complete recovery.
In general, it is advisable to totally refrain from drinking alcohol while
on antibiotics. Although drinking in moderation does not seem to
interact with the medication, patients should be advised to totally stop
drinking till a few days after the antibiotic regime is over or until they
recover totally from their illness. Patients should be aware of certain
sources of alcohol such as cold medicines or mouth washes when on
antibiotics.
Antibiotics in general have a tendency to interact with other
medications including complementary medicines as well as food and
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milk. Certain patients may get vomiting and diarrhea and it is
necessary to understand the interactions of antibiotics. As healthcare
providers we should be aware of various interactions of antibiotics
before we prescribe them to patients. In addition to interactions with
other drugs, antibiotics tend to destroy the gut flora. Thus, when a
health provider prescribes an antibiotic, it should be supplemented
with some probiotic to maintain the natural flora of the gut.
Antibiotic Resistance
Antibiotic resistance is becoming a global epidemic and a public health
problem spreading at an alarming rate. Now, with the increasing
prevalence of antibiotic resistant strains of bacteria, the ability to fight
a broad spectrum of infections seems to gradually reduce. Earlier, their
discovery not only saw a dramatic improvement of management and
treatment of many infections, but was considered a path breaking
discovery in the field of medicine. Currently, due to misuse, injudicious
and overuse of antibiotics, antibiotic resistance has emerged as a
major problem. Inaccurate use or repeated use of these drugs is the
main reason for primary resistant bacteria. This overuse threatens the
effectiveness of antibiotics in treating serious infections when in dire
need.
A growing concern is the increasing number of antibiotic resistant
cases in children. Very limited options are available for children and
they have the highest need for these drugs. So when antibiotics do not
work, illness lasts longer with extended hospital stay, more expenses
and use of more toxic medications. Mortality rates of life threatening
infections also increase with lesser effective antibiotics. A minimization
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of inappropriate usage of antibiotics is the only effective strategy to
tackle this rising crisis. Thus, antibiotic resistance not only seems to
affect health care directly, it also has strong economical and social
implications.
Some of the common reasons for the emergence of antibiotic
resistance are overuse of antibiotics, stopping antibiotic treatment
halfway during the prescribed course, and usage of antibiotics in
animals as growth enhancers. Increased international travel seems to
have led to an exponential rise in the reasons for antibiotic resistance.
Bacteria and Antibiotics
The credit for the discovery of antibiotics goes to Alexander Fleming,
who discovered the first antibiotic, penicillin. He observed that bacteria
could not survive on a plate of bread mold due to the presence of a
certain substance. This substance was identified by Fleming to be
penicillin, which he purified and started using for the treatment of
various bacterial agents.
What is Antibiotic Resistance?
Antibiotic resistance is said to have developed when the drug cannot
effectively fight against the bacteria that it formerly was effective
against, and is unable to prevent bacteria spread and growth. This
indicates that the bacteria have become resistant to the particular
antibiotic and continue to survive in spite of therapeutic levels of the
drug. These bacteria continue to proliferate and multiply even though
antibiotics are present in the circulation.
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Infections with drug resistant bacteria are extremely difficult to treat
and often require longer treatment, with higher blood levels to achieve
the therapeutic activity, which still might not help eradicate the
bacteria leading to fatal complications.
Why Bacteria Become Resistant to Antibiotics
Antibiotic resistance is a natural phenomenon. Bacteria become
resistant over a period of time because they become intrinsically
immune and continue to grow and multiply producing more antibiotic
resistant bacteria. This is simply a natural selection process of the
stronger bacteria over the entire population of bacteria. Bacteria learn
to adapt themselves as well as to evolve and survive.89 This means
that the bacterial genome or genetic component constantly improves
and changes with time. The non-functional part of the gene is removed
as the bacteria are constantly exposed to toxic doses of antibiotics. In
the process, survival of the fittest or resistant strains of bacteria
develop.
Mechanisms by which Bacteria become Resistant
Certain bacteria are naturally resistant to some classes of antibiotics.
The other two mechanisms90 by which these bacteria become resistant
to drugs are genetic mutations and acquired resistance, as discussed
below.
Genetic mutations are spontaneous changes that can occur one in a
ten million. Mutations happen at the genetic level, which produce slight
alterations in the DNA of the bacteria. Mutations91 are of various types
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and levels and, depending upon the change produced, they can affect
the effectiveness of the antibiotic. These mutations may either aid the
bacteria to release certain toxic chemicals, which can deactivate the
antibiotic, or destroy the target cells of antibiotics or even shut down
the entry ports for these antibiotics to reach their target cells. These
mutant bacteria have better survival rates over other bacteria due to
altered proteins or DNA in these cells only in the presence of antibiotic.
Some bacteria acquire resistance92 from some other bacteria through
the simple processes of mating or conjugation. Plasmids present in
bacterial cells help in the transfer of these resistant genes from one
bacteria to another. Viruses also serve as a vehicle for transmission of
these genes to the bacterium. They are normally packed in the head of
the virus. Bacteria also have an inherent ability of receiving free DNA
from the surrounding environment. This adaptation of swapping DNA is
a mechanism to survive in harsh environments.
Bacteria that have received these resistant genes either through
mutations or from other bacteria, are able to resist destruction by
various antibiotics. Over a period of time, bacteria receive a number of
resistant genes and soon become resistant to a number of antibiotics
and their various classes. In the presence of antibiotics and by natural
selection93 these mutant bacteria survive longer and prolong the
sickness. Although this mechanism is a kind of evolution, it leads to
greater losses of human life, cattle, etc. Though they are able to
survive longer in the environment, these bacteria are unable to
function efficiently, especially in the absence of antibiotics.
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Spread of Antibiotic Resistance
Antibiotic resistance spreads across populations of bacteria through
two ways:
 Vertical transfer:
Vertical transfer is a direct transfer of antibiotic resistant genes
from one generation to another.
 Horizontal transfer:
Horizontal transfer happens when bacteria share genetic
material across different bacterial species or from one bacteria to
another. These resistant bacteria can also travel from one place
to another through the air, or through people coughing or
sneezing. Thus, individuals too can transfer these bacteria from
one place to a completely new region.
Antibiotic resistant bacteria can lose its traits and reverse back, though
this process of losing resistance is much slower. It depends mainly on
removal of selective pressure94 that was applied, and then maybe
bacterial population can reverse back to being affected by antibiotics.
Certain Environments Prone to Antibiotic Resistance
For bacteria to become resistant, a couple of factors are obligatory,
such as a host to infect, which is mostly human beings or animals.
Additionally, heavy antibiotic use will facilitate natural selection and
loads of other bacteria to share these resistant genes. Thus, due to a
combination of these factors, there are certain environments that
encourage and promote antibiotic resistance. Hospitals are the perfect
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place for antibiotic resistant bacteria to develop and proliferate. They
fulfill all the above factors and, as a result, hospital acquired infections
are the most difficult to treat and manage. These infections cannot be
managed with standard antibiotic treatment. Hospitals that use too
many antibiotics along with improper sanitary conditions are the
primary source for breeding such strains of resistant bacteria.
Effects of Antibiotic Resistance
People tend to suffer longer and recover very slowly after an infection
with a drug resistant strain. Along with this, the cost of expense rises
tremendously and occasionally, these resistant infections can be fatal
for lack of any backup antibiotics that can successfully kill them.
Alternative drugs may be prescribed which may not only be more
toxic, but also more expensive. Maintaining the effectiveness of
antibiotics is extremely important to maintain human health.
Diagnostic Tests
Currently, diagnostic tests95 are available to not only determine which
bacteria is the causative agent, but also which antibiotics these
bacteria are resistant to. This will help the physician to choose the
correct antibiotic for treatment. Though, these tests take a long time
as they require the blood or tissue sample to be cultured96 and then
tested for sensitivity to these antibiotics. Thus the physician may not
have the time to wait till the results are out. He may need to start
treatment as soon as possible. The invariable immediate choice is a
wide spectrum antibiotic, which also triggers antibiotic resistance.
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Ways to Fight Antibiotic Resistance
A key approach is to prevent infections in the first place. It is
important to maintain good hygiene and sanitary habits to prevent
worsening of antibiotic resistance by practices such as hand washing,
safe food preparation and following immunization schedule. This itself
reduces the occurrence of infections and thereby the usage of
antibiotics. Use antibiotics only when required. Prevent spread of
infection along with the spread of resistant bacteria. Another approach
is to track resistant bacteria and infections. All information regarding
resistant infections and the spread of these should be accurately
recorded. A complete documentation of these helps the public health
bodies to devise particular strategies to combat and prevent these
resistant bacteria as well as infections.
Preventing undue use of antibiotics is the single most important
strategy for managing these infections is to stop the injudicious use
and overdosing of antibiotics. This itself will bring down antibiotic
resistance drastically. Broad-spectrum drugs should be avoided
wherever possible. Complete course of antibiotics should be taken
once initiated, should be taken only if required, and in the correct
dosage and at the right time.
New drugs and diagnostic tests are important for the clinician to be
informed about since developing resistance is a natural phenomena, it
cannot be totally stopped, but can be significantly reduced.
Development of new drugs to fight these bacteria and better
diagnostic tests to detect these resistant infections can greatly help to
tackle this situation. Antibiotic resistance can be overcome by
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developing potent drugs which are stronger and cannot be destroyed
and inactivated by enzymes of bacteria.
Antibiotic Resistance as a Social Health Problem
Since these mutant bacteria can pass from one bacteria to another, as
well as from one person to another, they can affect the whole
community en masse. This poses to be a major public health concern.
Since these bacteria can also spread to the environment through
waste products, they can also harm the environment. Once they enter
soil and water, they still have the ability to spread the resistant
bacterial genes to other bacteria present in the soil and water. The
overall burden of health care on the global economy has increased
dramatically due to such resistant strains, making it difficult to provide
even the basic means of treatment to the poorer strata of the society.
Accurate Method and Dosage of Antibiotic Therapy
As a health care community worker, we should be able to advise our
patients on when and how much antibiotics to take.
 Prudent use of antibiotics in the diagnosed cases of bacterial
infections and not common colds and flu.
 Prescriptions should be followed. The entire course of antibiotic
should be taken for a total elimination of bacteria. Leftover
antibiotics should not be used at all.
 Antibiotics when taken under medical guidance are usually safe
though occasionally can show some side effect or allergic
reaction. They can have interactions with other medications and
cause allergic reactions as well.
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A judicious use of antibiotics97 is advised to prevent the emergence of
widespread resistant bacteria, which cannot only affect humans as well
as animals. The enormous speed with which it spreads not only puts a
heavy toll on our pockets, but also increases mortality and morbidity
levels. Children, pregnant ladies and elders in the community are at a
higher risk.
Summary
The topic of bacterial virulence and pathogenicity are a major focus of
infectious disease research. This course discussed types of pathogens
and routes of transmission, and, in particular, theories of organism and
host relationship that include provocative and differing approaches to
antibiotic treatment. Generally, it is believed that the host determines
susceptibility to disease when exposed to a virulent organism more
than organism type or level of virulence. Immunocompromised
individuals are clearly more vulnerable than a healthy individual when
exposed to an invading bacteria, which is designed to replicate and can
endanger the health of a host. More specifically, the medical decision
to treat an infectious disease, whether through physical evaluation by
a skilled health provider and/or through laboratory testing, generally
involves use of an antibiotic drug selected by a provider based on
organism type and the level of patient immunity.
Over the years, antibiotic medications have improved and increased in
efficacy to kill harmful bacteria. Alternatively, the rising use of
antibiotics has led to the inability of hosts to effectively battle bacteria
due to antibiotic resistance that has developed as a result of
injudicious or overuse of antibiotics. Appropriate treatment of a
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bacterial infection involves understanding the synergism between the
organism and the host. It’s important that the medical practitioner
prescribing antibiotic treatment understand bacteria type and
bactericidal properties of agents needed to fight an offending bacteria
as well as the host environment. More studies are needed to examine
the collective interaction of antibiotics and the immune response of the
host, however, suffice it to say, health providers are recommended to
educate patients on the importance of maintaining healthy immunity
and to be cautious with the type and duration of antibiotic use to avoid
the harmful rise of resistant strains of bacteria to health.
Health providers must understand the pharmacokinetics and
pharmacodynamics of antibiotics as well as the natural and adaptive
immune responses of vulnerable populations. While it is important to
know the recommended antibiotic and host response to fight and to
clear infections, it is just as necessary to incorporate new knowledge
and to educate patients on emerging bacterial and antibiotic strains to
battle disease.
Please take time to help NurseCe4Less.com course planners
evaluate the nursing knowledge needs met by completing the
self-assessment of Knowledge Questions after reading the
article, and providing feedback in the online course evaluation.
Completing the study questions is optional and is NOT a course
requirement.
1. A pathogen can broadly be defined as a
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a.
b.
c.
d.
bacteria that invades the body.
viral infection.
*microorganism that has the ability to cause disease.
bacterial infection.
2. True or False: Lactobacilli help the body destroy pathogens
that make their way into the digestive system.
a. *True
b. False
3. Potential ways that antibiotics interact with contraception
pills is
a.
b.
c.
d.
in the acidic environment of the stomach.
*in the liver during metabolism.
normal flora in the bladder.
normal flora in the lower lung.
4. _____________ refers to a classification for the duration of
pathogens.
a.
b.
c.
d.
Communicable
Aerobic
*Chronic
Zoonotic
5. Antibiotic resistance is a natural phenomenon caused by
a. *the failure of patients to take their antibiotics as prescribed.
b. vertical transmission (parent to child).
c. the failure of patients to seek medical treatment as soon as the
infection symptoms appear.
d. healthcare personnel prescribing the wrong antibiotics.
6. The “normal flora” are microbes in the human body that
a.
b.
c.
d.
are safe even when a person’s immune system is weakened.
do not affect a person’s health.
are aerobic (not anaerobic) bacteria.
*are bound to parts of the body, i.e., the large intestine.
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7. True or False: Primary pathogens require an immunecompromised or injured host to cause disease.
a. True
b. *False
8. Primary pathogens have developed specialized mechanisms
a.
b.
c.
d.
that always lead to overt disease.
but they cannot cross cellular barriers.
*that contribute to the pathogen’s survival and multiplication.
that are never species specific.
9. ______________ is an example of a pathogen that causes
acute (not persistent) infections.
a.
b.
c.
d.
*Smallpox
Epstein Barr virus
Mycobacterium tuberculosis
Ascaris
10. Peritonitis primarily occurs when normal microorganisms
a.
b.
c.
d.
multiply because of a weakened immune system.
enter the peritoneal cavity due to a tick or flea bite.
*enter the peritoneal cavity of the abdomen.
have a duration that is chronic.
11. The ____________ is usually kept nearly sterile of normal
flora.
a.
b.
c.
d.
mouth
skin
*lower lung
small intestine
12. Peristalsis helps with
a.
b.
c.
d.
the adhesion of microorganisms.
parasites adhering to epithelial surfaces.
normal flora adhering to the small intestines.
*the periodic flushing (clearing) of microorganisms.
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13. _____________ do not have the capacity of carrying out
an independent metabolic activity.
a.
b.
c.
d.
*Viruses
Pathogens
Normal flora
Bacteria
14. __________ manufacture two types of toxins called
exotoxins and endotoxins.
a.
b.
c.
d.
Pathogens
*Bacteria
Fungi
Enteroviruses
15. A rare infectious particle known as a prion
a.
b.
c.
d.
can cause neurodegenerative diseases.
is made only of protein.
can replicate and kill the host.
*All of the above
16. True or False: Bacteria can successfully occupy ecological
places in extremes of temperature that have nutrient
limitations.
a. *True
b. False
17. Invasins are extracellular substances that
a.
b.
c.
d.
produce exotoxins.
*facilitate invasion of the host.
produce endotoxins.
affect neural tissue.
18. Bacterial adherence to a eukaryotic cell or tissue surface
require two factors:
a.
b.
c.
d.
an adhesin and a ligand.
*a receptor and a ligand.
an invasin and receptor.
peristalsis and adherence.
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19. Nonspecific adherence (the reversible attachment of the
bacteria to the eukaryotic surface) is sometimes referred
to as
a.
b.
c.
d.
anchoring.
involvement.
*docking.
colonization.
20. True or False: Commonly, nonspecific adherence or
reversible attachment will precede specific adherence or
irreversible attachment.
a. *True
b. False
21. Which pathogens have an outer membrane that is not
easily penetrated by hydrophobic compounds?
a.
b.
c.
d.
Lysozyme
Gram-positive bacteria
Spiral shaped bacteria
*Gram-negative bacteria
22. Host defense to bacteria include which of the following?
a.
b.
c.
d.
*Phagocytes
Capsids
Nucleocapsids
Lipopolysaccharides (LPS)
23. In enveloped viruses, the nucleocapsid is covered by
______________ membrane that the virus gains from the
host cell plasma membrane.
a.
b.
c.
d.
ribosome
lysing
*a lipid bilayer
lysozyme
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24. Protozoan parasites are eukaryotes and therefore
a.
b.
c.
d.
antifungal drugs are more effective than antibiotics.
antifungal drugs are made less toxic than antibiotics.
they have simple life cycles.
*it is more difficult to find a drug that will kill the pathogen
without killing the host.
25. True or False: Unlike exotoxins, which are discharged from
bacterial cells, endotoxins cannot be discharged by a
growing bacterial cell.
a. True
b. *False
26. Most of the important pathogenic fungi exhibit
dimorphism, which is the ability
a.
b.
c.
d.
*to grow in either yeast form or mold form.
to be ingested or inhaled.
to colonize a host.
to service more than one host.
27. More than 200-300 million people every year contract
__________, which causes 1-3 million deaths annually.
a.
b.
c.
d.
*Malaria
smallpox
poliomyelitis
the common cold
28. Medically, the virulence of a pathogen refers to
a.
b.
c.
d.
the ability of the organism to cause disease.
the fatality rates of a pathogen.
how dangerous a pathogen is to the host.
*All of the above
29. True or False: Virulence helps to differentiate pathogens
from non-pathogens.
a. *True
b. False
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30. Virulence refers to or is
a. *the capacity of an organism to produce disease.
b. heavily dependent upon the host's resistance.
c. an independent variable defined by the microbial's
characteristics.
d. the evolutionary history of microorganisms.
31. Virulence is a phenomenon which
a.
b.
c.
d.
varies according to both host and microbial factors.
depends exogenous factors such as medical intervention.
is still not clearly defined.
*All of the above
32. One of the attributes of virulence is “aggressiveness,”
which is the
a.
b.
c.
d.
way a pathogen transmits.
contagiousness of a pathogen.
*way a pathogen invades, survives and multiplies.
toxicity of a pathogen.
33. True or False: Many still do not recognize contagiousness
and transmission as attributes of virulence.
a. *True
b. False
34. According to studies in evolution, virulence tends to
increase in transmission
a.
b.
c.
d.
between parent-to-child.
between persons because of adherence to mucosal surfaces.
*between non-relatives.
vertically not horizontally.
35. “Capsule formation” is a virulence factor that refers to
a.
b.
c.
d.
invasion by colonization.
attachment to host cells.
*an organism avoiding host immune responses.
suppression of the host immune system.
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36. Virulence of many microbes is
a.
b.
c.
d.
not affected by the absence of host defense mechanisms.
*present even amongst immunized individuals.
not modified by intrinsic factors present in the host.
based on attributes of the microbe, not the host.
37. True or False: Virulence is universally accepted as a
characteristic of the microbe and not a separate factor.
a. True
b. *False
38. While virulence factors separate pathogenic from
nonpathogenic microbes, this does not explain
a.
b.
c.
d.
the absence of virulence amongst immunized persons.
why host damage occurs due to microbial characteristics only.
the presence of virulence amongst immunized individuals.
*why certain avirulent microbes can affect immunecompromised hosts.
39. Bactericidal drugs are used for specific infections, such as
a.
b.
c.
d.
*a staphylococcal aureus infection.
C. albicans infection.
malaria.
Mycobacterium tuberculosis.
40. The main aim of the use of antibiotics is
a.
b.
c.
d.
*to fight bacterial infections.
to encourage growth of normal flora.
to fight viral infections.
to fight most respiratory tract infections.
41. ______________ drugs kill the bacteria which come within
the sphere of action of that particular antibiotic.
a.
b.
c.
d.
Bacteriostatic
Oral antibiotic
*Bactericidal
Topical antibiotic
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42. Drugs such as quinolones and rifampin specifically inhibit
________ synthesis, thus limiting bacterial growth.
a.
b.
c.
d.
protein
folic acid
cell wall
*nucleic acid
43. IM injections have 100% bioavailability, but are rarely
used because
a.
b.
c.
d.
IM injections require hospitalization.
IM injections may only provide a single dose.
most drugs require larger doses than IM injections provide.
*of the pain they cause.
44. Pharmacokinetics as applied to antibiotics determines the
a. dose of a drug at the time of administration.
b. absorption but not the elimination of the drug by the host.
c. *level of an administered antibacterial agent in the host’s
serum or tissue over time.
d. best mode of administration of a drug (orally, intramuscularly,
or intravenously).
45. For an infection located in the cerebrospinal fluid,
a.
b.
c.
d.
*prolonged, parenteral antibiotics become necessary.
prolonged, oral antibiotics are most effective.
periodic IM injections work best.
an IV is the least effective mode of drug administration.
46. Taking the antibiotic metronidazole with alcohol can cause
a.
b.
c.
d.
a disulfiram like reaction.
nausea, cramping, and vomiting.
rapid heart rate as well as difficulty in breathing.
*All of the above
47. True or False: A major disadvantage of the use of
aminoglycosides is their renal toxicity.
a. *True
b. False
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48. Vancomycin is usually used as a second line treatment for
a.
b.
c.
d.
penicillin resistant Neisseria.
*staphylococci, enterococci, and streptococci infections.
gram-negative bacteria.
against anaerobic bacteria.
49. One of the potential side effects of vancomycin is that it
may
a.
b.
c.
d.
lead to permanent deafness.
*lead to “Red man syndrome.”
cause alteration of taste.
headaches and dizziness.
50. Aminoglycosides are the drugs of choice for
a.
b.
c.
d.
gram-negative bacteria.
*severe upper urinary tract infections.
anaerobic bacteria.
patients with impaired renal function.
51. Which of the following is the drug of choice for the
treatment of severe, invasive, group A streptococcal
infections?
a.
b.
c.
d.
Clarithromycin
Corynebacterium
Methicillin
*Clindamycin
52. The reason(s) for the emergence of antibiotic resistance
is/are
a.
b.
c.
d.
overuse of antibiotics.
stopping antibiotics halfway in the course.
usage of antibiotics in animals as growth enhancers.
*All of the above
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53. What antibiotic is rarely used in adult infections due to its
rare but dangerous side effect of irreversible bone marrow
aplasia?
a.
b.
c.
d.
Clindamycin
Tetracyclines
*Chloramphenicol
Ciprofloxacin
54. Serious infections caused by methicillin-resistant
staphylococci can be treated with ________ combined with
antibacterial agents.
a.
b.
c.
d.
*Rifampin
Metronidazole
Corynebacterium
Clarithromycin
55. True or False: Most of the colds, sore throats, respiratory
tract infections, ear infections, and sinus infections are
caused by bacteria.
a. True
b. *False
56. The following statement(s) are true about the use of
antibiotics to treat viruses:
a. The very definition of antibiotics itself clearly states that these
drugs act against bacteria.
b. An antibiotic’s spectrum of activity does not include viruses.
c. The use of antibiotics for viral infections is invariably a misuse
and potentially harmful.
d. *All of the above
57. Indiscriminate use of antibiotics for treating infections
a. is innocuous because antibiotics are always curative.
b. is not harmful because antibiotics do not attack beneficial
bacteria.
c. *promotes antibiotic-resistant bacteria.
d. is safe because it protects the people who come in contact with
the treated patient.
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58. Which of the following is a serious and sometimes fatal
side effect seen in patients being treated with
carbapenems?
a.
b.
c.
d.
*Allergic reactions
headaches and dizziness
Irreversible bone marrow aplasia
Nephrotoxicity
59. True or False: The most common use of antibiotics for
prophylaxis is following surgical procedures.
a. *True
b. False
60. A disadvantage of broad spectrum antibiotics is
a. they are not effective against viruses.
b. *they change the body's normal microbial content by attacking
beneficial microbes.
c. they have restricted activity and are effective against only one
general category of microorganisms.
d. they are only effective against gram-positive bacteria.
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CORRECT ANSWERS:
1. A pathogen can broadly be defined as
c. a microorganism that has the ability to cause disease.
“A pathogen can be defined as a microorganism that has the
ability to cause disease.”
2. True or False: Lactobacilli help the body destroy pathogens
that make their way into the digestive system.
a. True
“Lactobacilli help the body destroy pathogens that make their
way into the digestive system.”
3. Potential ways that antibiotics interact with contraception
pills is
b. in the liver during metabolism.
“There are two proposed mechanisms by which these
antibiotics are thought to interact with birth control pills. These
two potential ways by which antibiotic interaction can occur
with oral contraceptive pills is either in the liver during
metabolism or in the enterohepatic circulation through the
intestinal flora.”
4. _________ refers to a classification for the duration of
pathogens.
c. Chronic
“Duration of Infection: Another classification for various kinds
of pathogens is how long the infectious disease lasts. Most
infections constitute three major types: Acute; Latent;
Chronic.”
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5. Antibiotic resistance is a natural phenomenon caused by
a. the failure of patients to take their antibiotics as prescribed.
“Some of the common reasons for the emergence of antibiotic
resistance are overuse of antibiotics, stopping antibiotic
treatment halfway during the prescribed course, and usage of
antibiotics in animals as growth enhancers.”
6. The “normal flora” are microbes in the human body that
d. are bound to parts of the body, i.e., the large intestine.
“These thousands of types of microbes exist inside the human
body as normal flora, and are typically bound to certain parts
of the body, including the mouth, nose, skin, large intestine,
and vagina.”
7. True or False: Primary pathogens require an immunecompromised or injured host to cause disease.
b. False
“Notably, primary pathogens do not require an immunecompromised or injured host.”
8. Primary pathogens have developed specialized mechanisms
c. that contribute to the pathogen’s survival and multiplication.
“Primary pathogens have developed extremely specialized
mechanisms for crossing cellular and biochemical barriers and
for eliciting specific responses from the host organism that
contribute to the pathogen’s survival and multiplication.”
9. ______________ is an example of a pathogen that causes
acute (not persistent) infections.
a. Smallpox
“Some pathogens cause acute epidemic infections and have a
tendency to spread rapidly from one sick host to another;
historically, important examples are the smallpox and bubonic
plague.”
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10. Peritonitis primarily occurs when normal microorganisms
c. enter the peritoneal cavity of the abdomen.
“Normal microorganisms cause problems only if the immune
system is weakened or if they gain access to a sterile part of
the body; for example, peritonitis, where a bowel perforation
enables gut flora to enter the peritoneal cavity of the
abdomen…”
11. The ____________ is usually kept nearly sterile of normal
flora.
c. lower lung
“Additionally, the lining of the small intestine, the lower lung
and the bladder, are usually kept nearly sterile despite the
presence of a comparatively direct route to the external
environment.”
12. Peristalsis helps with
d. the periodic flushing (clearing) of microorganisms.
“The host epithelial cell lining of the upper gastrointestinal
tract and in the urinary bladder also has a thick layer of
mucus, and these microorganisms are periodically flushed by
peristalsis and by voiding, respectively.”
13. _____________ do not have the capacity of carrying out
an independent metabolic activity.
a. Viruses
“Viruses cause infectious diseases ranging from autoimmune
deficiency syndrome (AIDS) to smallpox to the common cold….
They do not have the capacity of carrying out an independent
metabolic activity and thus rely completely on metabolic
energy provided by the host.”
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14. __________ manufacture two types of toxins called
exotoxins and endotoxins.
b. Bacteria
“Bacteria manufacture two types of toxins called exotoxins and
endotoxins.”
15. A rare infectious particle known as a prion
a.
b.
c.
d.
can cause neurodegenerative diseases.
is made only of protein.
can replicate and kill the host.
*All of the above
“Some rare neurodegenerative diseases are caused by an
unusual type of infectious particle known as a prion, which is
made only of protein. Though the infectious particle prion
contains no genome, it can even replicate and kill the host.”
16. True or False: Bacteria can successfully occupy ecological
places in extremes of temperature that have nutrient
limitations.
a. True
“Bacteria … are far more diverse than eukaryotes, and they
can successfully occupy ecological places in extremes of
temperature and with nutrient limitations that may restrain
even the foremost intrepid eukaryote.”
17. Invasins are extracellular substances that
b. facilitate invasion of the host.
“The qualities by which pathogenic bacteria cause transmission
of disease are broadly divided into two types: … Invasiveness:
As the name suggests, it is the ability to invade tissues. It is
comprised of mechanisms for colonization, production of
invasins, which are extracellular substances that facilitate
invasion and the threshold to bypass or overcome the host
immune response or defense mechanisms.”
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18. Bacterial adherence to a eukaryotic cell or tissue surface
require two factors:
b. a receptor and a ligand.
“In the simplest type of bacterial adherence to a eukaryotic cell
or tissue surface, bacteria need the involvement of two factors:
a receptor and a ligand.”
19. Nonspecific adherence (the reversible attachment of the
bacteria to the eukaryotic surface) is sometimes referred
to as
c. docking.
“Nonspecific adherence - It is a reversible attachment of the
bacteria to the eukaryotic surface (sometimes referred as
‘docking’).”
20. True or False: Commonly, nonspecific adherence or
reversible attachment will precede specific adherence or
irreversible attachment.
a. True
“Commonly, it is seen that nonspecific adherence or reversible
attachment precedes specific adherence or irreversible
attachment.”
21. Which pathogens have an outer membrane that is not
easily penetrated by hydrophobic compounds?
d. Gram-negative bacteria
“In gram-negative bacteria, the outer membrane is a
formidable permeability barrier, which is not easily penetrated
by hydrophobic compounds like bile salts that are otherwise
harmful to the bacteria.”
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22. Host defense to bacteria include which of the following?
a. phagocytes
“Bacteria that invade tissues are firstly exposed to phagocytes.
It is seen that bacteria which readily attract phagocytes and
that are easily ingested and killed by them are not successful
as a parasite, and bacteria that are successful in interfering
with the activities of phagocytes or in some way avoid their
action are established as parasites.”
23. In enveloped viruses, the nucleocapsid is covered by
______________ membrane that the virus gains from the
host cell plasma membrane.
c. a lipid bilayer
“In enveloped viruses, the nucleocapsid is covered by a lipid
bilayer membrane, which the virus gains in the process of
growing from the host cell plasma membrane.”
24. Protozoan parasites are eukaryotes and therefore
d. it is more difficult to find a drug that will kill the pathogen
without killing the host.
“Many of the pathogenic fungi and protozoa are eukaryotes
and therefore it is more difficult to find a drug that will kill the
pathogen without killing the host.”
25. True or False: Unlike exotoxins, which are discharged from
bacterial cells, endotoxins cannot be discharged by a
growing bacterial cell.
b. False
“However, endotoxins can also be discharged by the growing
bacterial cells and cells that are attacked or destroyed by
effective host defense or by antibiotics.”
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26. Most of the important pathogenic fungi exhibit
dimorphism, which is the ability
a. to grow in either yeast form or mold form.
“Most of the important pathogenic fungi exhibit dimorphism;
which is the flexibility to grow in either yeast form or mold
form.”
27. More than 200-300 million people every year contract
__________, which causes 1-3 million deaths annually.
a. Malaria
“The most common example is Plasmodium, which causes
Malaria, which infects more that 200-300 million people every
year and causing death in 1-3 million of them.”
28. Medically, the virulence of a pathogen refers to
a.
b.
c.
d.
the ability of the organism to cause disease.
the fatality rates of a pathogen.
how dangerous a pathogen is to the host.
All of the above [correct answer]
“Medically, virulence can be defined as the ability of an
organism to invade the tissues of a host and produce the
disease. It is a measure to determine how dangerous a
pathogen is and to compare how aggressive different
pathogens or organisms may be. This can be judged from the
fatality rates and records, which show how many people fell
sick by the various strains of microbes.”
29. True or False: Virulence helps to differentiate pathogens
from non-pathogens.
a. True
“Virulence helps to differentiate pathogens from nonpathogens.”
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30. Virulence refers to or is
a. the capacity of an organism to produce disease.
“Virulence is usually measured by the ability of an organism to
produce disease in an animal.”
31. Virulence is a phenomenon which
a.
b.
c.
d.
varies according to both host and microbial factors.
depends on exogenous factors such as medical intervention.
is still not clearly defined.
All of the above [Correct answer]
“Virulence is not an independent variable, but remains heavily
dependent upon the host resistance as well as the interaction
of microbe and host, and thus cannot be solely known as a
microbial characteristic. Reduction in host defenses, which is
dependent upon numerous variables, is defined as pathogenic
virulence. Virulence is a complex and dynamic phenomenon
that varies according to both host and microbial factors. This
phenomenon depends upon other exogenous factors such as
medical intervention too…. Through studies and trials we hope
to underline the characteristics of virulence and quantify the
amount of host damage caused by the disease.”
32. One of the attributes of virulence is “aggressiveness,”
which is the
c. way a pathogen invades, survives and multiplies.
“The way the pathogens invade, survive and multiply was
another attribute of virulence known as aggressiveness.”
33. True or False: Many still do not recognize contagiousness
and transmission as attributes of virulence.
a. True
“These factors such as contagiousness and transmission are
still very complex in their relationship to virulence of
organisms. Many still do not clearly recognize these as definite
attributes of virulence, as there are many organisms that can
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cause life-threatening conditions, but are absolutely noncontagious.”
34. According to studies in evolution, virulence tends to
increase in transmission
c. between non-relatives.
“Many still do not clearly recognize these as definite attributes
of virulence, as there are many organisms that can cause lifethreatening conditions, but are absolutely non-contagious.
However, certain microorganisms in spite of adherence to
mucosal surfaces are not very virulent. According to studies in
evolution, virulence tends to increase in transmission between
non-relatives than between parent-to-child. This happens as
the fitness of the host is bound in vertical transmission but not
in horizontal transmission.”
35. “Capsule formation” is a virulence factor that refers to
c. an organism avoiding host immune responses.
“Avoiding host immune responses (capsule formation).”
36. Virulence of many microbes is
b. present even amongst immunized individuals.
“With the emerging antigenic variants, it can provide virulence
to many microbes even amongst immunized individuals.”
37. True or False: Virulence is universally accepted as a
characteristic of the microbe and not a separate factor.
b. False
“Virulence is not an independent variable, but remains heavily
dependent upon the host resistance as well as the interaction
of microbe and host, and thus cannot be solely known as a
microbial characteristic.”
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38. While virulence factors separate pathogenic from
nonpathogenic microbes, this does not explain
d. why certain avirulent microbes can affect immunecompromised hosts.
“Though it has been stated that virulence factors separate
pathogenic from nonpathogenic microbes, it cannot be
universally acknowledged. This does not explain the fact that
certain avirulent microbes can affect immune-compromised
hosts.”
39. Bactericidal drugs are used for specific infections, such as
a. a staphylococcal aureus infection.
“Though most of the treatments consist of bacteriostatic
variety of antibiotics, bactericidal drugs are used in specific
infections like complicated staphylococcal aureus infection and
in patients with altered immunity.”
40. The main aim of the use of antibiotics is
a. to fight bacterial infections.
“The main aim of the use of antibiotics is to fight bacterial
infections and the choice of the antibiotic depends on multiple
factors as detailed below.”
41. ______________ drugs kill the bacteria which come within
the sphere of action of that particular antibiotic.
c. Bactericidal
“Bacteriostatic … [drugs] stop the growth of bacteria, but do
not kill them.… Bactericidal … antibiotics directly kill the
bacteria.”
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42. Drugs such as quinolones and rifampin specifically inhibit
________ synthesis, thus limiting bacterial growth.
d. nucleic acid
“Quinolones, rifampin, nitrofurantoin and metronidazole inhibit
nucleic acid synthesis by hindering DNA gyrase activity,
making DNA replication impossible and thus limiting bacterial
growth.”
43. IM injections have 100% bioavailability, but are rarely
used because
d. of the pain they cause.
“Intramuscular (IM) injections show a 100% bioavailability, but
are rarely used due to the pain they cause….”
44. Pharmacokinetics as applied to antibiotics determines the
c. the level of an administered antibacterial agent in the host’s
serum or tissue over time.
“Pharmacokinetics refers to the level of the antibacterial agent
that is reached in the serum or tissue of the host following
administration over time.”
45. For an infection located in the cerebrospinal fluid,
a. prolonged, parenteral antibiotics become necessary.
“When infections are located in areas where the reach of
antibiotics is minimal or the site is protected that makes
penetration poor, i.e., cerebrospinal fluid, prostate, eye, or
cardiac vegetations, the use of parenteral antibiotics for a
prolonged period become necessary.”
46. Taking the antibiotic metronidazole with alcohol can cause
a.
b.
c.
d.
a disulfiram like reaction.
nausea, cramping, and vomiting.
rapid heart rate as well as difficulty in breathing.
All of the above [Correct answer]
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“One of the most common interactions of alcohol occurs with
metronidazole, which is commonly given for a number of
infections of skin, joints, respiratory tract and gastrointestinal
tract. Taking these drugs along with alcohol can cause a
disulfiram-like reaction, which includes nausea, cramping,
vomiting, rapid heart rate as well as difficulty in breathing.”
47. True or False: A major disadvantage of the use of
aminoglycosides is their renal toxicity.
a. True
“Aminoglycosides are the drugs of choice for severe upper
urinary tract infections with gentamycin and tobramycin being
generally preferred. However, the major disadvantage of the
use of aminoglycosides is their renal toxicity.”
48. Vancomycin is usually used as a second line treatment for
b. staphylococci, enterococci, and streptococci infections.
“Vancomycin: Its action is limited to gram-positive bacteria
and is usually chosen as a second line of treatment for
staphylococci, enterococci, and streptococci infections.
However, it is the drug of choice in infections caused by
Corynebacterium and methicillin resistant staphylococci.”
49. One of the potential side effects of vancomycin is that it
may
b. lead to “Red man syndrome.”
“Glycopeptides: Other antibiotics in this class include
vancomycin and telavancin. Vancomycin can lead to ‘Red man
syndrome’ whose symptoms are flushing or erythematous rash
affecting the face, neck and upper torso, itching and
hypotension. Other side effects that are seen due to
vancomycin are nephrotoxicity including renal failure and
interstitial nephritis, blood disorders including neutropenia. It
can also lead to deafness, that is reversed once the drug is
stopped. Telavancin causes alteration of taste, nausea,
vomiting, headache and dizziness.”
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50. Aminoglycosides are the drugs of choice for
b. severe upper urinary tract infections.
“Aminoglycosides are the drugs of choice for severe upper
urinary tract infections with gentamycin and tobramycin being
generally preferred.”
51. Which of the following is the drug of choice for the
treatment of severe, invasive, group A streptococcal
infections?
d. Clindamycin
“Clindamycin is the most widely used lincosamide owing to its
broad-spectrum activity against gram-positive and gramnegative anaerobes. Bacteria resistant to erythromycin are also
resistant to clindamycin. It is the drug of choice for the
treatment of severe, invasive, group A streptococcal
infections.”
52. The reason(s) for the emergence of antibiotic resistance
is/are
a.
b.
c.
d.
overuse of antibiotics.
stopping antibiotics halfway in the course.
usage of antibiotics in animals as growth enhancers.
All of the above [Correct answer]
“Some of the common reasons for the emergence of antibiotic
resistance are overuse of antibiotics, stopping antibiotic
treatment halfway during the prescribed course, and usage of
antibiotics in animals as growth enhancers.”
53. What antibiotic is rarely used in adult infections due to its
rare but dangerous side effect of irreversible bone marrow
aplasia?
c. Chloramphenicol
“Chloramphenicol: Its use is limited to the treatment of typhoid
fever, and is the drug of choice in pneumococcal and
meningococcal meningitis in patients with severe penicillin
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allergy. It is rarely used in adult infections due to its rare but
dangerous side effect of irreversible bone marrow aplasia.”
54. Serious infections caused by methicillin-resistant
staphylococci can be treated with ________ combined with
antibacterial agents.
a. Rifampin
“Rifampin: This drug is used in combination with other
antibacterial agents in the treatment of serious infections
caused by methicillin-resistant staphylococci.”
55. True or False: Most of the colds, sore throats, respiratory
tract infections, ear infections, and sinus infections are
caused by bacteria.
b. False
“Most of the colds, sore throats, respiratory tract infections,
ear infections, and sinus infections are caused by viruses.”
56. The following statement(s) are true about the use of
antibiotics to treat viruses:
a. The very definition of antibiotics itself clearly states that
these drugs act against bacteria.
b. An antibiotic’s spectrum of activity does not include viruses.
c. The use of antibiotics for viral infections is invariably a
misuse and potentially harmful.
d. All of the above [Correct answer]
“The very definition of antibiotics itself clearly states that these
drugs act against bacteria. Their spectrum of activity does not
include viruses at all. The use of antibiotics in any viral
infection is invariably a misuse leading to potential harm.”
57. Indiscriminate use of antibiotics for treating infections
c. promotes antibiotic-resistant bacteria.
“Indiscriminate use of antibiotics in infections where they are
not supposed to be used only promotes resistance
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development against the otherwise useful antibacterial
agents.”
58. Which of the following is a serious and sometimes fatal
side effect seen in patients being treated with
carbapenems?
a. Allergic reactions
“Serious and sometimes fatal allergic reactions may be seen in
patients being treated with carbapenems.”
59. True or False: The most common use of antibiotics for
prophylaxis is following surgical procedures.
a. True
“The most common use of antibiotics for prophylaxis is
following surgical procedures.”
60. A disadvantage of broad spectrum antibiotics is
b. they change the body's normal microbial content by
attacking beneficial microbes.
“As these have the ability to affect a wide species of organisms
in the body, as a side-effect, broad spectrum antibiotics can
amend the body's normal microbial content by attacking
indiscriminately both the pathological and naturally present,
healthy, beneficial or harmless microbes.”
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