types of pathogens, bacterial infection and antibiotic therapy

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TYPES OF PATHOGENS,

BACTERIAL INFECTION

AND

ANTIBIOTIC THERAPY

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 two of a 2-part series on

pathogens and 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

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 varied

types of 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

(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. 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. in the acidic environment of the stomach. b. in the liver during metabolism. c. normal flora in the bladder. d. normal flora in the lower lung.

4. _________ refers to a classification for the duration of

pathogens.

a. Communicable b. Aerobic c. Chronic d. 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

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: An Overview

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

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.1-3,16

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,

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.

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.1-3,16

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.

• 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.

• 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

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.

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.

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

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.

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.

The Body’s 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

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

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. 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.

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.1,2,13

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

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.

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

occupy ecological places in extremes of temperature and with nutrient

limitations that may restrain even the foremost intrepid eukaryote.

The qualities by which pathogenic bacteria and causes of transmission

are discussed in this section.1-3,13-15

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

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

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:

• Contact between phagocyte and microbial cell

• Engulfment

• Phagosome formation

• Phagosome lysosome fusion

• Killing and digestion

Toxigenesis

Exotoxins are discharged from bacterial cells and may act at tissue

sites far from the position of the bacterial growth. Endotoxins are cell-


associated 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.

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 ways viruses invade a host is

reviewed here.1,2,36

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

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

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.


Fungal And Protozoan Transmission Of Infection

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.1,2,48,49

Fungal and parasitic infections have a characteristic that makes them

tough to treat - 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

humans by the bite of the female of any species of the Anopheles

mosquito.

Virulence And Pathogenicity

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.1-3,12,13,21

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

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 Virulence

Virulence and pathogenicity are commonly overused terms amongst

microbiologists that are rather difficult to replace and clearly

demarcate. 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

Since virulence is recognized as a multifaceted characteristic of some

microbes, it is necessary to focus on the attributes of virulence.

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

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.

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.

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

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-to-

child. This happens as the fitness of the host is bound in vertical

transmission but not in horizontal transmission.

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.


Virulence Factors

This concept of virulence 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:

• 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 microorganisms 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

common ways to analyze and understand these factors are

biochemically, immunologically and genetically.

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 factors

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

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.

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.

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.

Antibiotic Therapy

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.12-14,21-28

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,

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 of Bacteriostatic Action

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

bacteriostatic action depending on the antibiotic in use. The drugs that


act in this way are aminoglycosides, macrolides, chloramphenicol and

linezolid.

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.

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%

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. When infections are

located in areas where the reach of antibiotics is minimal or the site is

protected that make 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.

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

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.

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

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 broad-

spectrum 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.

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. Metronidazole is also the drug of choice in the treatment of

bacterial vaginosis and antibiotic-associated pseudomembranous

colitis.

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. Viruses cause most of the colds,

sore throats, respiratory tract infections, ear infections, and sinus

infections. Viruses also cause many kinds of gastroenteritis. 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.

• 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.

Antibiotics And 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.

Antibiotics may also be given during the procedure and are continually

given after the surgery. The target organism is mostly staphylococcus

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.

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.


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.

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.

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.

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.

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

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. 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.

• As prophylaxis or preventive treatment after an operation, so as

to prevent infections.

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.


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 gram-

negative 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. Uses and advantages of narrow spectrum

antibiotics include:

• Prescription for a specific infection when the exact causative

organism is identified.

• Narrow spectrum antibiotics will not kill too many of the normal

microorganisms in the body as compared to the broad-spectrum

antibiotics; they are less likely to cause a superinfection.

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.

Choosing The 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

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.

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

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.

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.

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. The term narrow

spectrum agent is occasionally considered to be a synonym of targeted

microorganism therapy and an indicator of a medical clinician’s

concern for ecology. It has been stated that the diagnosis of an

infection as much 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.

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 broad-

spectrum 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.

Bacteria And 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, namely-

bactericidal and bacteriostatic based on their action on bacteria.4-6,21,22

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. 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.

Penicillins

The penicillins are one of the oldest antibiotics 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, which thereby prevents the bacteria’s cross-linking

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.

When compared, it has been observed that penicillin is more effective

against gram-positive bacteria than gram-negative bacteria as gram-

positive 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

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. 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

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 penicillin-

binding protein-1a. Aztreonam is not too effective against gram-

positive and anaerobic bacteria as it does not bind well with their

penicillin-binding proteins. Aztreonam has predominant action against

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.

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. 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

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.

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. 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.

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.

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.

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.

It binds specifically to A2451 and A2452 residues 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. 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

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.

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.6,12,13,21,22

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.


A broader way of classifying routes of administration is enteral and

parenteral. Enteral pertains to the gastrointestinal tract, which

includes 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.

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, such as 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.

The commonly prescribed route for administering antibiotics is

considered below.

• Oral: The most common route is oral.

• 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: The rectal 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

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): The IM route 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, 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, central venous line, endotracheal

tube implantable port, intra articular route, intracardiac route,

intraperitoneal route, intravesical route and umbilical artery or vein.

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. 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 solid and liquid forms. Solids

can be in the form of tablets or capsules and liquid form is often as

syrup.


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

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

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

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:

• 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.

• 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. 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


fluids of the skin and passes through the walls of nearby capillaries,

and is absorbed into the blood.

Intravenous

Drugs are given into a peripheral vein or by infusion. A bag of

intravenous (IV) 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.

Intravenous administration is usually carried out in one of three ways

listed below.

• 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.


Rapid injections are used in cases of epileptic seizures, cardiac

arrhythmias or acute asthma. Advantages include rapid response, total

dose/bioavailability and the amount of the dose give, as noted below:

• 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 finding a suitable vein, drug toxicity and cost of

administration of the drug:

• 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.


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 amoxicillin-clavulanate, ampicillin, and cefixime

generally cause antibiotic-associated diarrhea; also other antibiotics

like cephalosporins, fluoroquinolones, azithromycin, clarithromycin,

erythromycin, and tetracycline can cause diarrhea.

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)/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.


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.


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


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, amoxicillin-

clavulanate, 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. It is also seen that the patients who receive

antibiotics from the beta-lactam group have a 1% chance of

developing allergic reactions.


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.

Aminoglycosides:

Other antibiotics in this class include gentamicin, tobramycin,

amikacin.


Adverse effects caused due to aminoglycosides are mainly seen in

kidney and ear. Experimental data suggest that gentamicin is more

toxic than tobramycin and amikacin. Aminoglycosides cause acute

kidney injury, thereby causing a significant rise in serum creatinine

levels. 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 ototoxicity 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. Seizures can occur in people taking

imipenem and meropenem in limited doses. People being treated with

carbapenems can even suffer from diarrhea caused due to clostridium

difficile.

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.

Macrolides:

Other antibiotics in this class include erythromycin, azithromycin,

clarithromycin and roxithromycin.

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.

Sulfonamides:

Other antibiotics in this class include trimethoprin-sulfamethoxazole,

erythromycin-sulfisoxazole, and sulfadiazine.

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.

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.

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

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.


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

admitted to the emergency room. 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.13,14,21,22

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.

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 frequency 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, 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

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 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.


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. Rifampin 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 hormone-binding 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:

• Amount of estrogen and progesterone in the oral contraceptive

pill

• Dose and duration of antibiotic prescribed

• Fertility of couple

• Individual reaction of bacterial flora to drugs which can vary


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

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 rate 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

alcohol is still not clearly understood and only a few antibiotics seem to

have an interaction with alcohol.

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 consumption 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.

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, 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, 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-

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 drinks 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

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

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.


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. 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 mechanisms 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. Mutations are of various types

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 resistance 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

selection 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.


Spread of Antibiotic Resistance

Antibiotic resistance spreads across populations of bacteria through

two ways of vertical transfer and horizontal transfer.

• 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 pressure 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

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 and Causative Agent

Currently, diagnostic tests 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 clinician to choose the

correct antibiotic for treatment. These diagnostic tests take a long

time, as they require the blood or tissue sample to be cultured and

then tested for sensitivity to these antibiotics. Thus the physician may

not have the time to wait till the results are out. He/she may need to

start treatment as soon as possible. The invariable immediate choice is

a wide spectrum antibiotic, which also triggers antibiotic resistance.


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


developing potent drugs which are stronger and cannot be destroyed

and inactivated by enzymes of bacteria.

Antibiotic Resistance as a Public 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, clinicians should be able to advise

patients on when and how much antibiotics to take, and on the:

• 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.


A judicious use of antibiotics 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 clinician and/or

through laboratory testing, generally involves use of an antibiotic drug

selected by a clinician 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 bacterial infection involves understanding

the synergism between the organism and the host. It’s important that

the medical clinician 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

clinicians 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 clinicians 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 a. bacteria that invades the body. b. viral infection. 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. in the acidic environment of the stomach. b. in the liver during metabolism. c. normal flora in the bladder. d. normal flora in the lower lung.

4. _____________ refers to a classification for the duration of

pathogens.

a. Communicable b. Aerobic c. Chronic d. Zoonotic


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. are safe even when a person’s immune system is weakened. b. do not affect a person’s health. c. are aerobic (not anaerobic) bacteria. d. are bound to parts of the body, i.e., the large intestine.


7. True or False: Primary pathogens require an immune-compromised or injured host to cause disease.

a. True b. False

8. Primary pathogens have developed specialized mechanisms

a. that always lead to overt disease. b. but they cannot cross cellular barriers. c. that contribute to the pathogen’s survival and multiplication. d. that are never species specific.

9. ______________ is an example of a pathogen that causes

acute (not persistent) infections.

a. Smallpox b. Epstein Barr virus c. Mycobacterium tuberculosis d. Ascaris

10. Peritonitis primarily occurs when normal microorganisms

a. multiply because of a weakened immune system. b. enter the peritoneal cavity due to a tick or flea bite. c. enter the peritoneal cavity of the abdomen. d. have a duration that is chronic.

11. The ____________ is usually kept nearly sterile of normal

flora.

a. mouth b. skin c. lower lung d. small intestine

12. Peristalsis helps with

a. the adhesion of microorganisms. b. parasites adhering to epithelial surfaces. c. normal flora adhering to the small intestines. d. the periodic flushing (clearing) of microorganisms.


13. _____________ do not have the capacity of carrying out an independent metabolic activity.

a. Viruses b. Pathogens c. Normal flora d. Bacteria

14. __________ manufacture two types of toxins called

exotoxins and endotoxins.

a. Pathogens b. Bacteria c. Fungi d. Enteroviruses

15. A rare infectious particle known as a prion

a. can cause neurodegenerative diseases. b. is made only of protein. c. can replicate and kill the host. d. 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. produce exotoxins. b. facilitate invasion of the host. c. produce endotoxins. d. affect neural tissue.

18. Bacterial adherence to a eukaryotic cell or tissue surface

require two factors:

a. an adhesin and a ligand. b. a receptor and a ligand. c. an invasin and receptor. d. peristalsis and adherence.


19. Nonspecific adherence (the reversible attachment of the bacteria to the eukaryotic surface) is sometimes referred to as

a. anchoring. b. involvement. c. docking. d. 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. Lysozyme b. Gram-positive bacteria c. Spiral shaped bacteria d. Gram-negative bacteria

22. Host defense to bacteria include which of the following?

a. Phagocytes b. Capsids c. Nucleocapsids d. Lipopolysaccharides (LPS)

23. In enveloped viruses, the nucleocapsid is covered by

______________ membrane that the virus gains from the host cell plasma membrane.

a. ribosome b. lysing c. a lipid bilayer d. lysozyme


24. Protozoan parasites are eukaryotes and therefore

a. antifungal drugs are more effective than antibiotics. b. antifungal drugs are made less toxic than antibiotics. c. they have simple life cycles. d. 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. to grow in either yeast form or mold form. b. to be ingested or inhaled. c. to colonize a host. d. to service more than one host.

27. More than 200-300 million people every year contract

__________, which causes 1-3 million deaths annually.

a. Malaria b. smallpox c. poliomyelitis d. the common cold

28. Medically, the virulence of a pathogen refers to

a. the ability of the organism to cause disease. b. the fatality rates of a pathogen. c. how dangerous a pathogen is to the host. d. All of the above

29. True or False: Virulence helps to differentiate pathogens

from non-pathogens.

a. True b. False


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. varies according to both host and microbial factors. b. depends exogenous factors such as medical intervention. c. is still not clearly defined. d. All of the above

32. One of the attributes of virulence is “aggressiveness,”

which is the

a. way a pathogen transmits. b. contagiousness of a pathogen. c. way a pathogen invades, survives and multiplies. d. 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. between parent-to-child. b. between persons because of adherence to mucosal surfaces. c. between non-relatives. d. vertically not horizontally.

35. “Capsule formation” is a virulence factor that refers to

a. invasion by colonization. b. attachment to host cells. c. an organism avoiding host immune responses. d. suppression of the host immune system.


36. Virulence of many microbes is

a. not affected by the absence of host defense mechanisms. b. present even amongst immunized individuals. c. not modified by intrinsic factors present in the host. d. 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. the absence of virulence amongst immunized persons. b. why host damage occurs due to microbial characteristics only. c. the presence of virulence amongst immunized individuals. d. why certain avirulent microbes can affect immune-

compromised hosts. 39. Bactericidal drugs are used for specific infections, such as

a. a staphylococcal aureus infection. b. C. albicans infection. c. malaria. d. Mycobacterium tuberculosis.

40. The main aim of the use of antibiotics is

a. to fight bacterial infections. b. to encourage growth of normal flora. c. to fight viral infections. d. to fight most respiratory tract infections.

41. ______________ drugs kill the bacteria which come within

the sphere of action of that particular antibiotic.

a. Bacteriostatic b. Oral antibiotic c. Bactericidal d. Topical antibiotic


42. Drugs such as quinolones and rifampin specifically inhibit ________ synthesis, thus limiting bacterial growth.

a. protein b. folic acid c. cell wall d. nucleic acid

43. IM injections have 100% bioavailability, but are rarely

used because

a. IM injections require hospitalization. b. IM injections may only provide a single dose. c. most drugs require larger doses than IM injections provide. d. 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. prolonged, parenteral antibiotics become necessary. b. prolonged, oral antibiotics are most effective. c. periodic IM injections work best. d. an IV is the least effective mode of drug administration.

46. Taking the antibiotic metronidazole with alcohol can cause

a. a disulfiram like reaction. b. nausea, cramping, and vomiting. c. rapid heart rate as well as difficulty in breathing. d. All of the above

47. True or False: A major disadvantage of the use of

aminoglycosides is their renal toxicity.

a. True b. False


48. Vancomycin is usually used as a second line treatment for

a. penicillin resistant Neisseria. b. staphylococci, enterococci, and streptococci infections. c. gram-negative bacteria. d. against anaerobic bacteria.

49. One of the potential side effects of vancomycin is that it

may

a. lead to permanent deafness. b. lead to “Red man syndrome.” c. cause alteration of taste. d. headaches and dizziness.

50. Aminoglycosides are the drugs of choice for

a. gram-negative bacteria. b. severe upper urinary tract infections. c. anaerobic bacteria. d. 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. Clarithromycin b. Corynebacterium c. Methicillin d. Clindamycin

52. The reason(s) for the emergence of antibiotic resistance

is/are

a. overuse of antibiotics. b. stopping antibiotics halfway in the course. c. usage of antibiotics in animals as growth enhancers. d. All of the above


53. What antibiotic is rarely used in adult infections due to its rare but dangerous side effect of irreversible bone marrow aplasia?

a. Clindamycin b. Tetracyclines c. Chloramphenicol d. Ciprofloxacin

54. Serious infections caused by methicillin-resistant

staphylococci can be treated with ________ combined with antibacterial agents.

a. Rifampin b. Metronidazole c. Corynebacterium d. 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.


58. Which of the following is a serious and sometimes fatal side effect seen in patients being treated with carbapenems?

a. Allergic reactions b. headaches and dizziness c. Irreversible bone marrow aplasia d. 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.


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.”



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 immune-

compromised or injured host to cause disease.

b. False “Notably, primary pathogens do not require an immune-compromised 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.”


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.”


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. can cause neurodegenerative diseases. b. is made only of protein. c. can replicate and kill the host. d. 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.”


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.”


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.”


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. the ability of the organism to cause disease. b. the fatality rates of a pathogen. c. how dangerous a pathogen is to the host. d. 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 non-pathogens.”


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. varies according to both host and microbial factors. b. depends on exogenous factors such as medical intervention. c. is still not clearly defined. d. 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


cause life-threatening conditions, but are absolutely non-contagious.”

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 life-threatening 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.”


38. While virulence factors separate pathogenic from nonpathogenic microbes, this does not explain

d. why certain avirulent microbes can affect immune-compromised 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.”


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. a disulfiram like reaction. b. nausea, cramping, and vomiting. c. rapid heart rate as well as difficulty in breathing. d. All of the above [Correct answer]


“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.”


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 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.”

52. The reason(s) for the emergence of antibiotic resistance

is/are

a. overuse of antibiotics. b. stopping antibiotics halfway in the course. c. usage of antibiotics in animals as growth enhancers. d. 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


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


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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