TYPES OF PATHOGENS, BACTERIAL AND THERAPY

Jassin M. Jouria, MD

Dr. Jassin M. Jouria is a medical doctor, professor of academic , 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 & .

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 treatment for an infectious disease. This course is part two of a 2-part series on pathogens and therapy with a focus on general issues affecting antibiotic selection, the types of pathogens and diseases treated, and on specific ’ indication, administration and potential adverse effects. Antibiotic misuse and resistance is discussed. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1 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 . 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 1. A pathogen can broadly be defined as a

a. 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 . 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4 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 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 that cause infectious diseases, collectively termed as pathogens. More recently, the advent of microbial and molecular 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?

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7 • 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8 • 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10 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 by the host cell. Hitching a ride through the skin with the help of an insect nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11 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 or 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14 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, nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15 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 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16 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 and a . 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, nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17 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 . 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- nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20 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 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21 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 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 24 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. 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 25 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 28 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 29 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 30 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 31 , 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 32 act in this way are , , and .

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 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, 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 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 33 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 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 34 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 . Clarithromycin is the drug of choice in the treatment of gastric H. pylori infection in combination with a proton pump inhibitor.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35

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 . 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 36 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 37 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 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38 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,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 39 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 40 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 41 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 42 Imipenem, , 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 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 43 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 44 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 45 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46 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 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 47 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 48 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 49 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 , 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 50 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 51 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 . 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 52 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 53 The 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 54 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 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 55 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 56 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 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 .

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 57 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 58 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 59 • 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 60 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 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 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 61 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 62 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 63 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 64 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 65 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 66 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 67 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 . 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 .

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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 68 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 69 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 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 70 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 71 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 72 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 73 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 74 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 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 75 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, , and .

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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 76 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, , 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 77 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,

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 78 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 79 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 80 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 81 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 82 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 83 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 84 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 85 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 86 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 87 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 88 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 89 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 90 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 91 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 92 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 93 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 94 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 95 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 96 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. 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 97 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 98 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 99 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 100 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 101 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 102 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 103 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 104 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 105 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 106 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.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 107 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 108 5. Antibiotic resistance is a natural phenomenon caused by

a. the failure of patients to take their antibiotics as prescribed.

“Some of the common reasons for the emergence of antibiotic resistance are overuse of antibiotics, stopping antibiotic treatment halfway during the prescribed course, and usage of antibiotics in animals as growth enhancers.”

6. The “normal flora” are microbes in the human body that

d. are bound to parts of the body, i.e., the large intestine.

“These thousands of types of microbes exist inside the human body as normal flora, and are typically bound to certain parts of the body, including the mouth, nose, skin, large intestine, and vagina.”

7. True or False: Primary pathogens require an 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.” nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 109 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 110 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 111 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 112 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 113 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 114 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 115 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 116 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 117 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]

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 118 “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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 119 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 120 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

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 121 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.”

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 122 References Section

The reference section of in-text citations include published works intended as helpful material for additional reading.

• Alberts B, Johnson A, Lewis J, et al. New York, Molecular Biology of the Cell, 4th edition, Garland Science; 2002. • Liise-anne Pirofski and Arturo Casadevall. BMC Biology 2012, 10:6 http://www.biomedcentral.com/1741-7007/10/6 • Nikolaos, I, et al (2010). Dynamics of infectious disease transmission by inhalable respiratory droplets. J R Soc Interface. 2010 Se 6:7(50):1355-1366. • Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cho H, Uehara T, Bernhardt TG.Cell. 2014 Dec 4;159(6):1300-11. • Antibiotics that target protein synthesis. McCoy LS, Xie Y, Tor Y.Wiley Interdiscip Rev RNA. 2011 Mar-Apr;2(2):209-32. • Prospective multicentre feasibility study of a quality of care indicator for intravenous to oral switch therapy with highly bioavailable antibiotics. Buyle FM, Metz-Gercek S, et al. Antibiotic Strategy International-ABS Quality Indicators Team.J Antimicrob Chemother. 2012 Aug;67(8):2043-6. • Antibiotic dosing in cirrhosis. Halilovic J, Heintz BH.Am J Health Syst Pharm. 2014 Oct 1;71(19): 1621-34. Review. • β-lactam antibiotic concentrations during continuous renal replacement therapy. Beumier M, Casu GS, et al. Crit Care. 2014 May 22; 18(3): R105. • Catheter-related Corynebacterium bacteremia: should the catheter be removed and vancomycin administered? Ghide S, Jiang Y, et al. Eur J Clin Microbiol Infect Dis. 2010 Feb;29(2):153-6. Epub 2009 Dec 17. • Metronidazole treatment for acute phase amoebic liver abscess in patients co-infected with HIV. Ohnishi K, Uchiyama-Nakamura F. Int J STD AIDS. 2012 Aug; 23(8): e1-3. • Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. Kiran RP, Murray AC, et al. Surg. 2015 Sep; 262(3): 416-25; discussion 423-5. • The role of microbiological monitoring and drug history in the effectiveness of antibiotic prophylaxis and antibiotic treatment of infectious complications after reconstructive surgeries. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 123 Bogomolova ns, Kuznetsova sm, et al. 2015 mar-apr; 60(2): 20-6. • Surbhi Leekha, Christine L. Terrell, Randall S. Edson. General Principles of Antimicrobial Therapy, Mayo Clin Proc. 2011 Feb; 86(2): 156–167 • Jacquolyn G. Black, Microbiology Principles and Exploration 4/E. http://www.srspharma.com/narrow-spectrum-antibiotics.htm • Verstraeten N, Knapen W, Fauvart M, Michiels J. A Historical Perspective on Bacterial Persistence. Methods Mol Biol. 2016;1333:3-13. • Cho H, Uehara T, Bernhardt TG. Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cell. 2014 Dec 4;159(6):1300-11. • Badari MS, Elgendy SG, Mohamed AS, Hassan AT. Immunomodulatory Effects of Levofloxacin on Patients with Pneumonia in Assiut University Hospitals. Egypt J Immunol. 2015; 22(1):79-85. • Breilh D, Texier-Maugein J, Allaouchiche B, Saux MC, Boselli E. Carbapenems. J Chemother. 2013 Feb;25(1):1-17. • van Zuuren EJ, Fedorowicz Z. Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments. Br J Dermatol. 2015 Sep;173(3):651-62. Epub 2015 Aug 30. Review. • Schifano JM, Edifor R, Sharp JD; et al. Mycobacterial toxin MazF- mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site. Proceedings of the National Academy of Sciences of the United States of America.2013 May; 110: 8501– 6. • Susan M. Turley. Fourth edition, chapter 4. Routes of administration and the drug cycle. Understanding pharmacology for health professionals. Page 47-63. 2010. Pearson Education, Inc. http://www.boomer.org/c/p4/c07/c07.pdf, 2015 • Aschenbrenner Diane S., Venable Samantha J. Drug Administration. Drug Therapy in Nursing. 209, 29- 30. http://study.com/academy/lesson/routes-of-drug- administration-oral-topical-inhalation-injection.html, 2015 • http://textbookofbacteriology.net/antimicrobial.html, 2015 • http://www.nhs.uk/conditions/Antibiotics- penicillins/Pages/Introduction.aspx, 2015 • Gonzalez-Estrada, A; Radojicic, C (May 2015). Penicillin allergy: A practical guide for clinicians. Cleveland Clinic journal of medicine 82 (5): 295–300. • Prayle A1, Watson A, Fortnum H, Smyth A. Side effects of aminoglycosides on the kidney, ear and balance in cystic nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 124 fibrosis. Thorax. 2010 Jul;65(7):654-8. • Torres MJ, Blanca M (2010). "The complex clinical picture of beta-lactam hypersensitivity: penicillins, cephalosporins, monobactams, carbapenems, and clavams". Med. Clin. North Am. 94 (4): 805–20, xii. • Slimings C, Riley TV (2014). "Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis". J. Antimicrob. Chemother. 69(4): 881–91. • Qiuxang T, Ya Z, Jian L et al. Structure of the CCR5 chemokine receptor-HIV entry inhibitor Maraviroc complex. Science, 2013; 341:6152. • Evelien V, Fusun G, Zafer C et al. Novel inhibitors of influenza virus fusion-Activity relationship and interaction with viral hemaglutinin. J Virol. 2010; 84(9): 4277-4288. • Birkman A. Helicase-primase inhibitor pritelivir for HSV-2 infection. New England journal of Medicine. 2014; 370: 201- 210. • Christiane MH, Augustine G, Sheik HK et al. Ribavirin for Lassa fever postexposure prophylaxis. Emerg Infect Dis. 2010; 16(12): 2009-2011. • Chono K, Katsumata K, Suzuki H, Shiraki K et al. Synergistic activity of amenamevir (ASP2151) with nucleoside analogs against herpes simplex virus types 1 and 2 and varicella-zoster virus. Antiviral Res. 2013; 97: 154–160. • World Health Organization. WHO removes Nigeria from polio endemic list. Press release. September 2015. • Stéphane V, Mira J, Shaun K. et al. Controlling measles using supplemental immunization activities: A mathematical model to inform optimal policy. Vaccine. 2015; 33(10): 1291–1296. • Betáková T, Švancarová P. Role and application of RNA interference in replication of influenza viruses. ActaVirologica. 2013; 57(2): 97–104. • Motavaf M, Safari S, Alavian SM. Therapeutic potential of RNA interference: a new molecular approach to antiviral treatment for hepatitis C. Journal of Viral Hepatitis. 2012; 19(11):757– 765. • Deshpande PB, Dandagi P, Udupa N, Goal SV, Jain SS, Vasanth SG. Controlled release polymeric ocular delivery of acyclovir. Pharm Dev Technol. 2010; 15:369–78. • Boom-joon K. Hepatitis B mutation in relation to liver disease progression of Korean patient. World J Gastroenterol, 2014; 20(2) 460-467. • Perales C, Beach NM, Sheldon J, Domingo E: Molecular basis of interferon resistance in hepatitis C virus. CurrOpinVirol. 2014, nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 125 8:38-44. • Gotte M: Resistance to nucleotide analogue inhibitors of hepatitis C virus NS5B: Mechanisms and clinical relevance. Curr Opin Virol 2014, 8:104-108. • Kieffer TL, George S: Resistance to hepatitis C virus protease inhibitors. Curr Opin Virol. 2014, 8:16-21. • Vadlapudi, A.D., Vadlapatla, R.K., and Mitra, A.K. Current and emerging antivirals for the treatment of cytomegalovirus (CMV) retinitis: an update on recent patents. Recent Pat. Antiinfect. Drug Discov. 7:8–18, 2012. • Zachary, K. (2016). Pharmacology of antiviral drugs for influenza. UpToDate. Retrieved online at https://www.uptodate.com/contents/pharmacology-of-antiviral- drugs-for- influenza?source=search_result&search=antiviral%20agents&sel ectedTitle=5~150. • Horn D, Duraisingh MT. Antiparasitic chemotherapy – from genomes to mechanisms. Annu Rev Pharmacol Toxicol. 2014:71-94. doi:10.1146/annurev-pharmtox-011613-135915. • Who. WHO | Malaria. Available at: http://www.who.int/mediacentre/factsheets/fs094/en/index.htm l • Mugnier MR, Cross GAM, Papavasiliou FN. The in vivo dynamics of antigenic variation in Trypanosoma brucei. Science. 2015;347(6229):1470-1473. doi:10.1126/science.aaa4502. • Jones JL, Parise ME, Fiore AE. Neglected parasitic infections in the United States: toxoplasmosis. Am J Trop Med Hyg. 2014;90(5):794-799. doi:10.4269/ajtmh.13-0722. • Esch KJ, Petersen CA. Transmission and epidemiology of zoonotic protozoal diseases of companion animals. Clin Microbiol Rev. 2013;26(1):58-85. doi:10.1128/CMR.00067-12. • Dufour AC, Olivo-Marin J-C, Guillen N. Amoeboid movement in protozoan pathogens. Semin Cell Dev Biol. 2015. doi:10.1016/j.semcdb.2015.10.010. • Legua P, Seas C. Cystoisospora and cyclospora. Curr Opin Infect Dis. 2013;26(5):479-483. doi:10.1097/01.qco.0000433320.90241.60. • Grace E, Asbill S, Virga K. Naegleria fowleri: Pathogenesis, Diagnosis, and Treatment Options. Antimicrob Agents Chemother. 2015;59(11):6677-6681. doi:10.1128/AAC.01293- 15. • Wang Y, Feng X, Jiang L. Current advances in diagnostic methods of Acanthamoeba keratitis. Chin Med J (Engl). 2014;127(17):3165-3170. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 126 • Lorenzo-Morales J, et al (2013). Is Balamuthia mandrillaris a public health concern worldwide? Trends Parasitol. 2013;29(10):483-488. doi:10.1016/j.pt.2013.07.009. • Silva C V, Costa-Cruz JM. A glance at Taenia saginata infection, diagnosis, vaccine, biological control and treatment. Infect Disord Drug Targets. 2010;10(5):313-321. • Thompson RCA. Neglected zoonotic helminths: Hymenolepis nana, Echinococcus canadensis and Ancylostoma ceylanicum. Clin Microbiol Infect. 2015;21(5):426-432. doi:10.1016/j.cmi.2015.01.004. • Hibberd, P., and Hirsch, M. (2016). Seasonal influenza vaccination in adults. UpToDate. Retrieved online at https://www.uptodate.com/contents/seasonal-influenza- vaccination-in- adults?source=search_result&search=influenza%20virus%20vac cine&selectedTitle=1~150 • Monath, T. (2016). Yellow Fever, UpToDate. https://www.uptodate.com/contents/yellow- fever?source=search_result&search=yellow%20fever%20virus&sele ctedTitle=1~150. • Colley DG, Bustinduy AL, Secor WE, King CH. Human schistosomiasis. Lancet (London, England). 2014;383(9936):2253-2264. doi:10.1016/S0140- 6736(13)61949-2. • Nyindo M, Lukambagire A-H. Fascioliasis: An Ongoing Zoonotic Trematode Infection. Biomed Res Int. 2015;2015:786195. doi:10.1155/2015/786195. • Petney TN, Andrews RH, Saijuntha W, Wenz-Mucke A, Sithithaworn P. The zoonotic, fish-borne liver flukes Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini. Int J Parasitol. 2013;43(12-13):1031-1046. doi:10.1016/j.ijpara.2013.07.007. • Blair D. Paragonimiasis. Adv Exp Med Biol. 2014;766:115-152. doi:10.1007/978-1-4939-0915-5_5. • Das AK. Hepatic and biliary ascariasis. J Glob Infect Dis. 2014;6(2):65-72. doi:10.4103/0974-777X.132042. • Vleeschouwers W, Hofman P, Gillardin JP, Meert V, Van Slycke S. Appendicitis-like clinical image elicited by Enterobius vermicularis: case report and review of the literature. Acta Chir Belg. 2013;113(2):139-142. • Toledo R, Munoz-Antoli C, Esteban J-G. Strongyloidiasis with emphasis on human infections and its different clinical forms. Adv Parasitol. 2015;88:165-241. doi:10.1016/bs.apar.2015.02.005. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 127 • Kappagoda S, Singh U, Blackburn BG. Antiparasitic therapy. Mayo Clin Proc. 2011;86(6):561-83. doi:10.4065/mcp.2011.0203. • Robertson AP, Buxton SK, Puttachary S, et al. Antinematodal Drugs – Modes of Action and Resistance: And Worms Will Not Come to Thee (Shakespeare: Cymbeline: IV, ii). In: Parasitic Helminths. Wiley-VCH Verlag GmbH & Co. KGaA; 2012:233-249. doi:10.1002/9783527652969.ch14. • Bahmani M, Rafieian-Kopaei M, Hassanzadazar H, Saki K, Karamati SA, Delfan B. A review on most important herbal and synthetic antihelmintic drugs. Asian Pac J Trop Med. 2014;7S1:S29-33. doi:10.1016/S1995-7645(14)60200-5. • Brunetti E, Kern P, Vuitton DA. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop. 2010;114(1):1-16. doi:10.1016/j.actatropica.2009.11.001. • Martinez DY, Seas C, Bravo F, et al. Successful treatment of Balamuthia mandrillaris amoebic infection with extensive neurological and cutaneous involvement. Clin Infect Dis. 2010;51(2):e7-11. doi:10.1086/653609. • World Health Organization. Guidelines for the Treatment of Malaria. 2015, 3rd Ed Geneva. 2015. • Dondorp AM, Fanello CI, Hendriksen ICE, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet (London, England). 2010;376(9753):1647-1657. doi:10.1016/S0140-6736(10)61924-1. • Kennedy PG. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol. 2013;12(2):186-194. doi:10.1016/S1474- 4422(12)70296-X. • Van Griensven J, Boelaert M. Combination therapy for visceral leishmaniasis. Lancet (London, England). 2011;377(9764):443- 444. doi:10.1016/S0140-6736(10)62237-4. • Collinet-Adler S, Ward HD. Cryptosporidiosis: environmental, therapeutic, and preventive challenges. Eur J Clin Microbiol Infect Dis. 2010;29(8):927-935. doi:10.1007/s10096-010- 0960-9. • Institute for Quality and Efficiency in Health Care. Using medication_ Oral medications. Natl Libr Med - PubMed Heal. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072625/. • Hibberd, P. (2016). Immunizations in HIV-infected patients. UpToDate. Retrieved online at nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 128 https://www.uptodate.com/contents/immunizations-in-hiv- infected- patients?source=search_result&search=HIV%20vaccine&selecte dTitle=1~129. • Chandrasekar P, Management of invasive fungal infections: a role for polyenes, The journal of antimicrobial chemotherapy, 2011 Mar;66(3):457-65. doi: 10.1093/jac/dkq479. • Loyes A, Thangaraj H, Easterbrook P, Ford N, Roy M, Chiller T, Govender N ... Bicanic T. (2013) Cryptococcal meningitis: improving access to essential antifungal medicines in resource- poor countries. Lancet Infect. Dis., 13(7), pp. 629-637. • Cuenca-Estrella M, Verweij PE, Arendrup MC et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. ClinMicrobiol Infect 2012; 18 (Suppl 7): 9–18. • Alastruey-Izquierdo A, Mellado E, Pelaez T et al. Population- based survey of filamentous fungi and antifungal resistance in Spain (FILPOP Study). Antimicrob Agents Chemother 2013; 57: 3380–3387. • Jesús F. Aparicio, Eva G. Barreales, Tamara D. Payero, Cláudia M. Vicente, Antonio de Pedro, Javier Santos-Aberturas. (2015) Biotechnological production and application of the antibiotic pimaricin: biosynthesis and its regulation. Applied Microbiology and Biotechnology. • Rotta I, Sanchez A, Gonçalves PR, Otuki MF, Correr CJ. Efficacy and safety of topical antifungals in the treatment of dermatomycosis: a systematic review. Br J Dermatol. 2012; 166(5): 927–933 • Jeans AR, Howard SJ, Al-Nakeeb Z Et al. Pharmacodynamics of voriconazole in a dynamic in vitro model of invasive pulmonary aspergillosis: implications for in vitro susceptibility breakpoints. J Infect Dis 2012; 206: 442–452. • Sanjay G. Revankar, Jack D. Sobel, Antifungal drugs, Merc’s manual (professional version), 2014. • Vale-Silva L, Ischer F, Leibundgut-Landmann S, Sanglard D. Gain-of-function mutations in PDR1, a regulator of antifungal drug resistance in Candida glabrata, control adherence to host cells. Infect Immun 2013; 81: 1709–1720. • Tang, M. M., Corti, M. A. M., Stirnimann, R., Pelivani, N., Yawalkar, N., Borradori, L. and Simon, Dec. 2012, Severe cutaneous allergic reactions following topical antifungal therapy. Contact Dermatitis, 68: 56–57. doi: 10.1111/j.1600- 0536.2012.02151.x • Leroux-Roels, Geert, et al. (2011). Understanding Modern nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 129 Vaccines: Perspectives in Vaccinology. Chapter 5: Science Direct. Elseviere; Volume 1, Issue 1. Retrieved online at http://www.sciencedirect.com/science/article/pii/S22107622110 00064. • Modlin, J.F., et al. (2016). Poliovirus vaccination. UpToDate. Retrieved online at https://www.uptodate.com/contents/poliovirus- vaccination?source=search_result&search=oral%20polio%20vac cine&selectedTitle=5~87. • Sax, P. (2016). Clinical trials of HIV antiretroviral therapy: Integrase inhibitors. UpToDate. Retrieved online at https://www.uptodate.com/contents/clinical-trials-of-hiv- antiretroviral-therapy-integrase- inhibitors?source=search_result&search=wild- type&selectedTitle=2~7. • Kozal, M. (2016). Drug resistance testing in the clinical management of HIV infection. UpToDate. Retrieved online at https://www.uptodate.com/contents/drug-resistance-testing-in- the-clinical-management-of-hiv- infection?source=search_result&search=viral%20drug%20resist ance&selectedTitle=2~150.

The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NurseCe4Less.com. The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare.

The information provided in this course is general in nature, and is not designed to address any specific situation. This publication in no way absolves facilities of their responsibility for the appropriate orientation of healthcare professionals.

Hospitals or other organizations using this publication as a part of their own orientation processes should review the contents of this publication to ensure accuracy and compliance before using this publication.

Hospitals and facilities that use this publication agree to defend and indemnify, and shall hold NurseCe4Less.com, including its parent(s), subsidiaries, affiliates, officers/directors, and employees from liability resulting from the use of this publication.

The contents of this publication may not be reproduced without written permission from NurseCe4Less.com.

nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 130