A brief description to antibiotic uses in chemistry.It includes almost every thing related to antibiotic chemistry

1. 1
ACKNOWLEDGEMENT
The ―Dissertation on Antibiotics‖ could not have turned out into a successful
dissertation without the kind support and help of many individuals and the collage
itself. I would like to extend my sincere thanks to all of them.
I am highly indebted to Medi Planet *Instiute of Medical Sciences * for their
guidance and constant supervision as well as for providing necessary information
regarding the dissertation and also for their support in completing it.
Our thanks and appreciations also go to the colleague in preparing the
dissertation and people who have willingly helped us out with their abilities.
The last but not the least, a very special thanks to our parents and relatives for
their moral support which gave us strength to make it.

2. 2
ABSTRACT
The consequences of bacterial infections have been curtailed by the
introduction of a wide range of antibiotics. However, infections continue to be a
leading cause of mortality, in part due to the evolution and acquisition of
antibiotic-resistance genes. Antibiotic misuse and over prescription have created
a driving force influencing the selection of resistance. Despite the problem of
antibiotic resistance in infectious bacteria, little is known about the diversity,
distribution and origins of resistance genes, especially for the uncultivable
majority of environmental bacteria. Functional and sequence-based met
genomics have been used for the discovery of novel resistance determinants and
the improved understanding of antibiotic-resistance mechanisms in clinical and
natural environments. This review discusses recent findings and future challenges
in the study of antibiotic resistance through met genomic approaches.

3. 3
Table of Contents
Acknowledgement i
Abstract ii
1 Introduction 1
1.1 Types of antibiotics 2
1.2 Classification 3
1.3 Using antibiotics 3
2 History 5
2.1 Medical uses of Antibiotics 7
2.2 Treatment 7
2.3 Prevention of infection 11
2.4 Antimicrobial pharmacodynamics 13
3 List of antibiotics 15
3.1 Classes 15
3.2 Antibiotic use in livestock 36
3.3 Drug and growth stimulation 37
3.4 Use in different livestock 38
4 Production of antibiotics 40
4.1 Identifying useful antibiotics 41
4.2 Industrial production techniques 41

4. 4
5 Adminstration 43
5.1 The topical antibiotics 43
5.2 Topical medications that act as
Comedolytics as well as antibiotics
69
6 Antibiotic resistance 75
6.1 Antimicrobial resistance 76
6.2 Causes 78
6.3 Environmental impact 82
6.4 Mechanisms 83
6.5 Organisms 86
6.6 Prevention 92
6.7 Applications 98
7 Status of New Antibiotics Development 99
8 Side-Effects & Misuse 117
8.1 Side-effects 117
8.2 Misuse 118
Conclusion 123
Reference 125

5. 5
Chapter – 1
Introduction
Antibiotics or antibacterial are a type of antimicrobial used in the treatment and
prevention of bacterial infection. They may either kill or inhibit the growth of bacteria. Several
antibiotics are also effective against fungi and protozoans, and some are toxic to humans and
animals, even when given in therapeutic dosage. Antibiotics are not effective
against viruses such as the common or influenza, and may be harmful when taken
inappropriately.
Antibiotics are medications used to treat, and in some cases prevent, bacterial
infections.They can be used to treat relatively mild conditions such as acne as well as potentially
life-threatening conditions such as pneumonia.However, antibiotics often have no benefit for
many other types of infection and using them unnecessarily would only increase the risk
ofantibiotic resistance, so they are not routinely used. Antibiotics revolutionized medicine in the
20th century, and have together with vaccination led to the near eradication of diseases such
as tuberculosis in the developed world. Their effectiveness and easy access led to overuse,
especially in live-stock raising, prompting bacteria to develop resistance. This has led to
widespread problems with antimicrobial and antibiotic resistance, so much as to prompt
the World Health Organization to classify antimicrobial resistance as a "serious threat is no
longer a prediction for the future, it is happening right now in every region of the world and has
the potential to affect anyone, of any age, in any country".
The era of antibacterial chemotherapy began with the discovery of arsphenamine, first
synthesized by Alfred Bertheim and Paul Ehrlich in 1907, used to treat syphilis. The first
systemically active antibiotic, prontosil was discovered in 1933 by Gerhard Domagk, for which
he was awarded the 1939 Nobel Prize.Sometimes the term antibiotic is used to refer to any
substance used against microbes, synonymous to antimicrobial. Some sources distinguish
between antibacterial and antibiotic; antibacterials used in soaps and cleaners etc., but not as
medicine. This article treats the terms as synonymous and according to the most widespread
definition of antibiotics being a substance used against bacteria.

6. 6
The first antibiotic was penicillin. Such penicillin-related antibiotics as ampicillin,
amoxicillin and benzylpenicilllin are widely used today to treat a variety of infections - these
antibiotics have been around for a long time.
There is concern worldwide that antibiotics are being overused. Antibiotic overuse is one
of the factors that contribute towards the growing number of bacterial infections which are
becoming resistant to antibacterial medications.According to the CDC (Centers for Disease
Control and Prevention), The ECDC (European Centre for Disease Prevention and Control) says
that antibiotic resistance continues to be a serious public health threat worldwide. In a statement
issued in 19th November 2012, the ECDC informed that an estimated 25,000 people die each
year in the European Union from antibiotic-resistant bacterial infections.
New ECDC data has shown that there has been a considerable increase over the last four
years of combined resistance to multiple antibiotics in E. coli and Klebsiella pneumoniae in over
one third of EU and EEA (European Economic Area) nations. Consumption of carbapenems, a
major class of last-line antibiotics, increased significantly from 2007 to 2010. Then there is the
danger that the ignorant man may easily underdose himself and by exposing his microbes to non-
lethal quantities of the drug, make them resistant," said Alexander Fleming, speaking in his
Nobel Prize acceptance speech in 1945. As predicted almost 70 years ago by the man who
discovered the first antibiotic, drug resistance is upon us.
1.1Types of antibiotics
Although there are a number of different types of antibiotic they all work in one of two ways:
 A bactericidal antibiotic kills the bacteria. Penicillin is a bactericidal. A bactericidal usually
either interferes with the formation of the bacterium's cell wall or its cell contents.
 A bacteriostatic stops bacteria from multiplying.
An antibiotic is given for the treatment of an infection caused by bacteria. Antibiotics
target microorganisms such as bacteria, fungi and parasites. However, they are not effective
against viruses. If you have an infection it is important to know whether it is caused by bacteria
or a virus. Most upper respiratory tract infections, such as the common cold and sore throats are
generally caused by viruses - antibiotics do not work against these viruses. If antibiotics are

7. 7
overused or used incorrectly there is a risk that the bacteria will become resistant - the
antibiotic becomes less effective against that type of bacterium.
A broad-spectrum antibiotic can be used to treat a wide range of infections. A narrow-
spectrum antibiotic is only effective against a few types of bacteria. There are antibiotics that
attack aerobic bacteria, while others work against anaerobic bacteria. Aerobic bacteria need
oxygen, while anaerobic bacteria don't. Antibiotics may be given beforehand, to prevent
infection, as might be the case before surgery. This is called 'prophylactic' use of antibiotics.
They are commonly used before bowel and orthopedic surgery.
1.2Classifications
A common scheme of classifications for antibiotics is drawn below:
Antibiotics can also be classified based on their chemical structure. A similar level of
effectiveness, toxicity and side-effects is rendered by the antibiotics of same structural group.
Broad spectrum antibiotics are effective against a broad range of microorganisms in comparison
to narrow spectrum antibiotics. Bactericidal antibiotics kill the bacteria whereas bacteriostatic
antibiotics halt the growth of bacteria.
1.3Using antibiotics
Antibiotics are usually taken by mouth (orally); however, they can also be administered
by injection, or applied directly to the affected part of the body.Most antibiotics start having an

8. 8
effect on an infection within a few hours. It is important to remember to complete the whole
course of the medication to prevent the infection from coming back.
If you do not complete the course, there is a higher chance the bacteria may become
resistant to future treatments - because the ones that survive when you did not complete the
course have had some exposure to the antibiotic and may consequently have built up a resistance
to it. Even if you are feeling better, you still need to complete the course.Some antibiotics should
not be consumed with certain foods and drinks. Others should not be taken with food in your
stomach - these would normally be taken about an hour before meals, or two hours after. It is
crucial that you follow the instructions correctly if you want the medication to be effective. If
you are taking metronidazole do not consume alcohol.Dairy products should not be consumed if
you are taking tetracyclines, as they might affect the absorption of the medication.

9. 9
Chapter – 2
History
Before the early 20th century, treatments for infections were based primarily
on medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of
infections were described over 2000 years ago. Many ancient cultures, including the ancient
Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to
treat infections. More recent observations made in the laboratory of antibiosis between
microorganisms led to the discovery of natural antibacterials produced by microorganisms. Louis
Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it
would offer perhaps the greatest hopes for therapeutics". The term 'antibiosis', meaning "against
life", was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of
the phenomenon exhibited by these early antibacterial drugs. Antibiosis was first described in
1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could
inhibit the growth of Bacillus anthracis. These drugs were later renamed antibiotics by Selman
Waksman, an American microbiologist, in 1942. Synthetic antibiotic chemotherapy as a science
and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s. Ehrlich
noted certain dyes would color human, animal, or bacterial cells, whereas others did not. He then
proposed the idea that it might be possible to create chemicals that would act as a selective drug
that would bind to and kill bacteria without harming the human host. After screening hundreds of
dyes against various organisms, in 1907, he discovered a medicinally useful drug, the synthetic
antibacterial salvarsan now called arsphenamine.
Fig: Penicillin, the first natural antibiotic discovered byAlexander Fleming in 1928

10. 10
The effects of some types of mold on infection had been noticed many times over the
course of history. In 1928, Alexander Fleming noticed the same effect in a Petri dish, where a
number of disease-causing bacteria were killed by a fungus of the genus Penicillium. Fleming
postulated that the effect is mediated by an antibacterial compound he named penicillin, and that
its antibacterial properties could be exploited for chemotherapy. He initially characterized some
of its biological properties, and attempted to use a crude preparation to treat some infections, but
he was unable to pursue its further development without the aid of trained chemists.
The first sulfonamide and first commercially available antibacterial, Prontosil, was
developed by a research team led by Gerhard Domagk in 1932 at the Bayer Laboratories of
the IG Farbenconglomerate in Germany. Domagk received the 1939 Nobel Prize for
Medicine for his efforts. Prontosil had a relatively broad effect against Gram-positive cocci, but
not againstenterobacteria. Research was stimulated apace by its success. The discovery and
development of this sulfonamide drug opened the era of antibacterials.
In 1939, coinciding with the start of World War II, Rene Dubos reported the discovery of
the first naturally derived antibiotic, tyrothricin, a compound of 20% gramicidin and
80% tyrocidine, fromB. brevis. It was one of the first commercially manufactured antibiotics
universally and was very effective in treating wounds and ulcers during World War
II. Gramicidin, however, could not be used systemically because of toxicity. Tyrocidine also
proved too toxic for systemic usage. Research results obtained during that period were not shared
between the Axis and the Allied powers during the war.
Florey and Chain succeeded in purifying the first penicillin, penicillin G, in 1942, but it
did not become widely available outside the Allied military before 1945. The chemical structure
of penicillin was determined by Dorothy Crowfoot Hodgkin in 1945. Purified penicillin
displayed potent antibacterial activity against a wide range of bacteria and had low toxicity in
humans. Furthermore, its activity was not inhibited by biological constituents such as pus, unlike
the synthetic sulfonamides. The discovery of such a powerful antibiotic was unprecedented, and
the development of penicillin led to renewed interest in the search for antibiotic compounds with
similar efficacy and safety. For their successful development of penicillin, which Fleming had
accidentally discovered but could not develop himself, as a therapeutic drug, Ernst
Chain and Howard Florey shared the 1945 Nobel Prize in Medicine with Fleming. Florey

11. 11
credited Dubos with pioneering the approach of deliberately and systematically searching for
antibacterial compounds, which had led to the discovery of gramicidin and had revived Florey's
research in penicillin.
2.1 Medical uses of Antibiotics
 Treatment
1. Bacterial infection
2. Protozoan infection, e.g., metronidazole and Bactrim is effective against
several parasitics
3. Immunomodulation, e.g., tetracycline, which is effective in periodontal inflammation,
and dapsone, which is effective inautoimmune diseases such as oral mucous
membrane pemphigoid.
4. Nonoperative resource for patients who have non-complicated acute appendicitis.
Treatment with antibiotics has proven to work, with almost no cases of remission.
 Prevention of infection
5. Surgical wound
6. Dental antibiotic prophylaxis
7. Conditions of neutropenia, e.g. cancer-related
2.2 Treatment
1. Bacterial infection
Pathogenic bacteria are bacteria that can cause infection. This article deals with human
pathogenic bacteria.Although most bacteria are harmless or often beneficial, several
are pathogenic. One of the bacterial diseases with the highest disease burden is tuberculosis,
caused by the bacterium Mycobacterium tuberculosis, which kills about 2 million people a year,
mostly in sub-Saharan Africa. Pathogenic bacteria contribute to other globally important
diseases, such as pneumonia, which can be caused by bacteria such
as Streptococcusand Pseudomonas, and foodborne illnesses, which can be caused by bacteria

12. 12
such asShigella, Campylobacter, and Salmonella. Pathogenic bacteria also cause infections such
as tetanus, typhoid fever, diphtheria, syphilis, and leprosy.
Bacterial infections may be treated with antibiotics, which are classified as bacteriocidal if
they kill bacteria or bacteriostatic if they just prevent bacterial growth. There are many types of
antibiotics and each class inhibits a process that is different in the pathogen from that found in
the host. For example, the antibiotics chloramphenicol and tetracyclin inhibit the
bacterial ribosome but not the structurally different eukaryotic ribosome, so they exhibit
selective toxicity.
Antibiotics are used both in treating human disease and in intensive farming to promote
animal growth. Both uses may be contributing to the rapid development of antibiotic
resistance in bacterial populations. Phage therapy can also be used to treat certain bacterial
infections. Infections can be prevented by antisepticmeasures such as sterilizing the skin prior to
piercing it with the needle of a syringe and by proper care of indwelling catheters. Surgical and
dental instruments are also sterilized to prevent infection by bacteria. Disinfectants such
as bleach are used to kill bacteria or other pathogens on surfaces to prevent contamination and
further reduce the risk of infection. Bacteria in food are killed by cooking to temperatures above
73 °C (163 °F)
2. Protozoan infection
Protozoan infections are parasitic diseases organisms formerly classified in the
Kingdom Protozoa. They include organisms classified in Amoebozoa, Excavata,
andChromalveolata. Examples include Entamoeba histolytica, Plasmodium (some of which
cause malaria), and Giardia lamblia. Trypanosoma brucei, transmitted by the tsetse fly and the
cause of African sleeping sickness, is another example. The species traditionally collectively
termed "protozoa" are not closely related to each other, and have only superficial similarities
(eukaryotic, unicellular, motile, though with exceptions.) The terms "protozoa" (and protist) are
usually discouraged in the modern biosciences. However, this terminology is still encountered in
medicine. This is partially because of the conservative character of medical classification, and
partially due to the necessity of making identifications of organisms based upon appearances and

13. 13
not upon DNA.Protozoan infections in animals may be caused by organisms in the sub-
class Coccidia(disease: Coccidiosis) and species in the genus Besnoitia (disease: Besnoitiosis).
They are treated with antiprotozoal agents. Recent papers have also proposed the use
of viruses to treat infections caused by protozoa.
Immunotherapy is the "treatment of disease by inducing, enhancing, or suppressing an
immune response".Immunotherapies designed to elicit or amplify an immune response are
classified as activation immunotherapies, while immunotherapies that reduce or suppress are
classified as suppression immunotherapies.
3. Tetracycline (Immunomodulation)
Tetracycline is a broad-spectrum polyketide antibiotic produced by the Streptomyces
genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein
synthesis inhibitor. It is commonly used to treat acne today, and, more recently, rosacea, and is
historically important in reducing the number of deaths from cholera. Tetracycline is marketed
under the brand names Sumycin, Tetracyn, Lymecycline, and Panmycin, among others. Actisite
is a thread-like fiber formulation used in dental applications. It is also used to produce several
semisynthetic derivatives, which together are known as the tetracycline antibiotics. The term
"tetracycline" is also used to denote the four-ring system of this compound; "tetracyclines" are
related substances that contain the same four-ring system.
 Use of the tetracycline antibiotics group is problematic; they can:]
Discolor permanent teeth (yellow-gray-brown), from infancy and childhood to eight years
old
Be inactivated by Ca2+
ion, so are not to be taken with milk, yogurt, and other dairy products
Be inactivated by aluminium, iron and zinc, not to be taken at the same time
as indigestion remedies (common antacids and over-the-counter heartburn medicines)
Cause skin photosensitivity, so exposure to the sun or intense light is not recommended
Cause drug-induced lupus, and hepatitis
Cause microvesicular fatty liver

14. 14
Cause tinnitus
Interfere with methotrexate by displacing it from the various protein binding sites
Cause breathing complications, as well as anaphylactic shock, in some individuals
Affect bone growth of the fetus, so should be avoided during pregnancy
Fanconi syndrome may result by ingesting expired tetracyclines.
Caution should be exercised in long-term use with breastfeeding. Short-term use is safe;
bioavailability in milk is low to nil. According to the U.S. FDA, there are case reports
of Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme associated
with doxycyline use but a causative role has not been established.
 Other uses
Since tetracycline is absorbed into bone, it is used as a marker of bone growth
for biopsies in humans. Tetracycline labeling is used to determine the amount of bone growth
within a certain period of time, usually a period of approximately 21 days. Tetracycline is
incorporated into mineralizing bone and can be detected by its fluorescence. In "double
tetracycline labeling", a second dose is given 11–14 days after the first dose, and the amount of
bone formed during that interval can be calculated by measuring the distance between the two
fluorescent labels.
Tetracycline is also used as a biomarker in wildlife to detect consumption of medicine-
orvaccine-containing baits. In genetic engineering, tetracycline is used in transcriptional
activation. It is also one of the antibiotics used to treat ulcers caused by bacterial infections. In
cancer research at Harvard Medical School, tetracycline has been used to switch off leukemia in
genetically altered mice, and to do so reliably, when added to their drinking water.
A technique being developed for the control of the mosquito species Aedes aegypti uses a
strain that is genetically modified to require tetracycline to develop beyond the larval stage.
Modified males raised in a laboratory will develop normally as they are supplied with this
chemical and can be released into the wild. Their subsequent offspring will inherit this trait, but
will find no tetracycline in their environment and so will never develop into adults.

15. 15
2.3 Prevention of infection
Preventive healthcare (alternately preventive medicine or prophylaxis) consists of
measures taken for disease prevention, as opposed to disease treatment. Just
as health encompasses a variety of physical and mental states, so do disease and disability, which
are affected by environmental factors, genetic predisposition, disease agents, and lifestyle
choices. Health, disease, and disability are dynamic processes which begin before individuals
realize they are affected. Disease prevention relies on anticipatory actions that can be categorized
as primary, secondary, and tertiary prevention.
Each year, millions of people die preventable deaths. A 2004 study showed that about
half of all deaths in the United States in 2000 were due to preventable behaviors and exposures.
Leading causes included cardiovascular disease, chronic respiratory disease, unintentional
injuries, diabetes, and certain infectious diseases. This same study estimates that 400,000 people
die each year in the United States due to poor diet and a sedentary lifestyle. According to
estimates made by the World Health Organization (WHO), about 55 million people died
worldwide in 2011, two thirds of this group from non-communicable diseases,
including cancer, diabetes, and chronic cardiovascular and lung diseases. This is an increase
from the year 2000, during which 60% of deaths were attributed to these diseases. Preventive
healthcare is especially important given the worldwide rise in prevalence of chronic diseases and
deaths from these diseases.
There are many methods for prevention of disease. It is recommended that adults and
children aim to visit their doctor for regular check-ups, even if they feel healthy, to perform
disease screening, identify risk factors for disease, discuss tips for a healthy and balanced
lifestyle, stay up to date with immunizations and boosters, and maintain a good relationship with
a healthcare provider.
Some common disease screenings include checking for hypertension (high blood
pressure), hyperglycemia , hypercholesterolemia (high blood cholesterol), screening for colon
cancer, depression, HIV and other common types of sexually transmitted disease such
as chlamydia, syphilis, and gonorrhea, mammography (to screen for breast cancer), colorectal
cancer screening, a pap test (to check for cervical cancer), and screening for osteoporosis.
Genetic testing can also be performed to screen for mutations that cause genetic disorders or

16. 16
predisposition to certain diseases such as breast or ovarian cancer. However, these measures are
not affordable for every individual and the cost effectiveness of preventive healthcare is still a
topic of debate.
1. Surgical incision
In surgery, a surgical incision is a cut made through the skin to facilitate
an operation or procedure. Often, multiple incisions are possible for an operation. In general, a
surgical incision is made as small and unobtrusive as possible to facilitate safe and timely
operating conditions.
2. Dental antibiotic prophylaxis
Dental antibiotic prophylaxis is the administration of antibiotics to a dental patient for
prevention of harmful consequences ofbacteremia, that may be caused by invasion of
the oral flora into an injured gingival or peri-apical vessel during dental treatment. This issue
remains a subject under constant revision, with the intention of providing recommendations
based on sound scientific evidence.
Currently, there are official guidelines for dental antibiotic prophylaxis for the prevention
of infective endocarditis and of infection of prosthetic joint. These guidelines are in constant
controversy and revisions by various professional committees. In addition, there are various
medical conditions for which clinicians recommended antibiotic prophylaxis, although there is
no evidence to support this practice.
These conditions include renal dialysis shunt, cerebrospinal fluid shunt, vascular
graft, immunosuppression secondary tocancer and cancer chemotherapy, systemic lupus
erythematosus, and type 1 diabetes mellitus.

17. 17
3. Neutropenia
Neutropenia or neutropaenia, from Latin prefix neutro- ("neither", for neutral staining)
and Greek suffix -πενία (-penía, "deficiency"), is a granulocyte disorder characterized by an
abnormally low number of neutrophils. Neutrophils usually make up 60 to 70% of
circulating white blood cells and serve as the primary defense against infections by
destroying bacteria in the blood. Hence, patients with neutropenia are more susceptible to
bacterial infections and, without prompt medical attention, the condition may become life-
threatening and deadly (neutropenic sepsis).
Neutropenia can be acute or chronic depending on the duration of the illness. A patient
has chronic neutropenia if the condition lasts longer than three months. It is sometimes used
interchangeably with the term leukopenia ("deficit in the number of white blood cells"), as
neutrophils are the most abundant leukocytes, but neutropenia is more properly considered a
subset of leukopenia as a whole.The numerous causes of neutropenia can roughly be divided
between problems in the production of the cells by the bone marrow and destruction of the cells
elsewhere in the body. Treatment depends on the nature of the cause, and emphasis is placed on
the prevention and treatment of infection.
2.4Antimicrobial pharmacodynamics
Antimicrobial pharmacodynamics is the relationship between concentration of antibiotic
and its ability to inhibit vital processes of endo- or ectoparasites and microbial organisms. This
branch of pharmacodynamics relates concentration of an anti-infective agent to effect, but
specifically to its antimicrobial effect.
 Concentration-dependent effects
The minimum inhibitory concentration and minimum bactericidal concentration are used
to measure in vitro activity antimicrobial and is an excellent indicator of antimicrobial potency.

18. 18
They don't give any information relating to time-dependent antimicrobial killing the so-called
post antibiotic effect.
 Post Antibiotic Effect
The post antibiotic effect (PAE) is defined as persistent suppression of bacterial growth
after a brief exposure (1 or 2 hours) of bacteria to an antibiotic even in the absence of host
defense mechanisms. Factors that affect the duration of the post antibiotic effect include duration
of antibiotic exposure, bacterial species, culture medium and class of antibiotic. It has been
suggested that an alteration of DNA function is possibly responsible for post antibiotic effect
following the observation that most inhibitors of protein and nucleic acid synthesis
(aminoglycosides, fluoroquinolones, tetracyclines, clindamycin, certain newer
macrolides/ketolides, and rifampicin and rifabutin) induce long-term PAE against susceptible
bacteria. Theoretically, the ability of an antibiotic to induce a PAE is an attractive property of an
antibiotic since antibiotic concentrations could fall below the MIC for the bacterium yet retain
their effectiveness in their ability to suppress the growth. Therefore, an antibiotic with PAE
would require less frequent administration and it could improve patient adherence with regard to
pharmacotherapy.
 Pharmacodynamics
The successful outcome of antimicrobial therapy with antibacterial compounds depends
on several factors. These include host defense mechanisms, the location of infection, and the
pharmacokinetic and pharmacodynamic properties of the antibacterial. A bactericidal activity of
antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic
activity and division of bacterial cells. These findings are based on laboratory studies, and in
clinical settings have also been shown to eliminate bacterial infection. Since the activity of
antibacterials depends frequently on its concentration, in vitro characterization of antibacterial
activity commonly includes the determination of the minimum inhibitory concentration and
minimum bactericidal concentration of an antibacterial. To predict clinical outcome, the
antimicrobial activity of an antibacterial is usually combined with its pharmacokinetic profile,
and several pharmacological parameters are used as markers of drug efficacy.

19. 19
Chapter 3
List of antibiotics
The following is a list of antibiotics, sorted by class. The highest division is
between bactericidal antibiotics and bacteriostaticantibiotics. Bactericidals kill bacteria directly,
whereas bacteriostatics prevent them from dividing. However, these classifications are based on
laboratory behavior. In practice, both can effectively treat a bacterial infection.
3.1Classes
Antibacterial antibiotics are commonly classified based on their mechanism of action,
chemical structure, or spectrum of activity. Most target bacterial functions or growth
processes. Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell
membrane (polymyxins), or interfere with essential bacterial enzymes have bactericidalactivities.
Those that target protein synthesis (macrolides, lincosamides and tetracyclines) are
usuallybacteriostatic (with the exception of bactericidal aminoglycosides). Further categorization
is based on their target specificity. "Narrow-spectrum" antibacterial antibiotics target specific
types of bacteria, such asGram-negative or Gram-positive bacteria, whereas broad-spectrum
antibiotics affect a wide range of bacteria. Following a 40-year hiatus in discovering new classes
of antibacterial compounds, four new classes of antibacterial antibiotics have been brought into
clinical use: cyclic lipopeptides (such asdaptomycin), glycylcyclines , oxazolidinones (such
as linezolid), and lipiarmycins(such as fidaxomicin).

20. 20
 Antibiotics by class
Generic name Brand names Common uses
Possible side
effects
Mechanism of
action
Aminoglycosides
Amikacin Amikin Infections caused
by Gram-negative
bacteria, such
asEscherichia
coli andKlebsiella partic
ularlyPseudomonas
aeruginosa. Effective
against Aerobic bacteria
(not obligate/facultative
anaerobes)
and tularemia. All
aminoglicocydes are
ineffective to be taken
orally. Intravenous,
intramuscular and topical
should be applied.
Hearing
loss
Vertigo
Kidney
damage
Binding to the
bacterial30S ribo
somal subunit
(some work by
binding to
the 50S subunit),
inhibiting the
translocation of
the peptidyl-
tRNA from the
A-site to the P-
site and also
causing
misreading of
mRNA, leaving
the bacterium
unable to
synthesize
proteins vital to
its growth.
Gentamicin Garamycin
Kanamycin Kantrex
Neomycin Neo-Fradin
Netilmicin Netromycin
Tobramycin Nebcin
Paromomycin Humatin
Streptomycin Tuberculosis
Spectinomycin(Bs Trobicin Gonorrhea

21. 21
Ansamycins
Geldanamycin
Experimental,
as antitumor antibiotics
Herbimycin
Rifaximin Xifaxan
Traveler's
diarrhea caused byE. coli
Carbacephem
Loracarbef Lorabid Discontinued
prevents
bacterial cell
division by
inhibiting cell
wall synthesis.
Carbapenems
Ertapenem Invanz
Bactericidal for both
Gram-positive and
Gram-negative
organisms and therefore
useful for empiric broad-
spectrum antibacterial
coverage. (Note MRSA
resistance to this class.)
Gastrointe
stinal
upset and
diarrhea
Nausea
Seizures
Headache
Rash and
allergic
reactions
Inhibition of cell
wall synthesis
Doripenem Doribax
Imipenem/Cilastat
in
Primaxin
Meropenem Merrem
Cephalosporins (First generation)

22. 22
Cefadroxil Duricef
Good coverage against
Gram-positive infections.
Gastrointe
stinal
upset and
diarrhea
Nausea (if
alcohol
taken
concurrent
ly)
Allergic
reactions
Same mode of
action as
other beta-
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell
walls.
Cefazolin Ancef
Cefalotin or Cefal
othin
Keflin(discontin
ued)
Cefalexin Keflex
Cephalosporins (Second generation)
Cefaclor Distaclor
Less Gram-positive
cover, improved Gram-
negative cover.
Gastrointe
stinal
upset and
diarrhea
Nausea (if
alcohol
taken
concurrent
ly)
Allergic
reactions
Same mode of
action as
other beta-
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell
walls.
Cefamandole
Mandol(disconti
nued)
Cefoxitin
Mefoxin(disconti
nued)
Cefprozil Cefzil
Cefuroxime
Ceftin, Zinnat(U
K)
Cephalosporins (Third generation)
Cefixime (antagon
istic with
Chloramphenicol)
Suprax
Improved coverage of
Gram-negative
organisms,
Gastrointe
stinal
upset and
Same mode of
action as
other beta-

23. 23
Cefdinir Omnicef, Cefdiel exceptPseudomonas.
Reduced Gram-positive
cover. But still not
cover Mycoplasma andC
hlamydia
diarrhea
Nausea (if
alcohol
taken
concurrent
ly)
Allergic
reactions
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell
walls.
Cefditoren
Spectracef,
Meiact
Cefoperazone [Unl
ike most third-
generation agents,
cefoperazone is
active
againstPseudomon
as aeruginosa],
combination
Cefoperazone
withSulbactam ma
kes more effective
antibiotic, because
Sulbactam avoid
degeneration of
Cefoperazone
Cefobid(disconti
nued)
Cefotaxime Claforan
Cefpodoxime Vantin
Ceftazidime [Unli
ke most third-
generation agents,
ceftazidime is
active
against Pseudomo
nas aeruginosa,
Fortaz

24. 24
but less active
against
staphylococci and
streptococci
compare to other
3rd generation of
Cephalosporins][5]
Ceftibuten Cedax
Ceftizoxime
Cefizox
(discontinued)
Ceftriaxone [IV
and IM, not orally,
effective also
for syphilisand
uncomplicated gon
orrhea]
Rocephin
Cephalosporins (Fourth generation)
Cefepime Maxipime Covers pseudomonal
infections.
Gastrointe
stinal
upset and
diarrhea
Nausea (if
alcohol
taken
concurrent
ly)
Allergic
Same mode of
action as
other beta-
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell

25. 25
reactions walls.
Cephalosporins (Fifth generation)
Ceftaroline
fosamil
Teflaro Used to treat MRSA
Gastrointe
stinal
upset and
diarrhea
Allergic
reaction
Same mode of
action as
other beta-
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell
walls.
Ceftobiprole Zeftera
Used to
treat MRSA(methicillin-
resistant Staphylococcus
aureus), penicillin-
resistant Streptococcus
pneumoniae,
Pseudomonas
aeruginosa, and
enterococci
Gastrointe
stinal
upset and
diarrhea
Nausea (if
alcohol
taken
concurrent
ly)
Allergic
reactions
Same mode of
action as
other beta-
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell
walls.
Glycopeptides
Teicoplanin Targocid (UK) Active against aerobic inhibiting peptid

26. 26
Vancomycin Vancocin and anaerobic Gram-
positive bacteria
including MRSA;
Vancomycin is used
orally for the treatment
of C. difficile
oglycansynthesis
Telavancin Vibativ
Dalbavancin Dalvance
Oritavancin Orbactiv
Lincosamides(Bs)
Clindamycin Cleocin Serious staph-, pneumo-,
and streptococcal
infections in penicillin-
allergic patients, also
anaerobic infections;
clindamycin topically
for acne
Possible C.
difficile-
relatedpseudo
membranous
enterocolitis
Bind to 50S
subunit of
bacterial
ribosomal RNAt
hereby inhibiting
protein synthesis
Lincomycin Lincocin
Lipopeptide
Daptomycin Cubicin Gram-positive organisms
Bind to the
membrane and
cause rapid
depolarization,
resulting in a
loss of
membrane
potential leading
to inhibition of
protein, DNA
and RNA
synthesis

27. 27
Macrolides(Bs)
Azithromycin
Zithromax,Suma
med,Xithrone
Streptococcal
infections,syphilis, upper
respiratory tract
infections, lower
respiratory tract
infections,mycoplasmal
infections, Lyme disease
Nausea,
vomiting,
and
diarrhea
(especially
at higher
doses)
Prolonged
cardiacQT
interval(es
pecially
erythromy
cin)
Hearing
loss
(especially
at higher
doses)
Jaundice
inhibition of
bacterialprotein
biosynthesis by
binding
reversibly to the
subunit 50S of
the
bacterial riboso
me, thereby
inhibiting
translocation of
peptidyltRNA.
Clarithromycin Biaxin
Dirithromycin
Dynabac(discont
inued)
Erythromycin
Erythocin,Erythr
oped
Roxithromycin
Troleandomycin
Tao
(discontinued)
Telithromycin Ketek Pneumonia
Visual
Disturbance,
Liver Toxicity.
Spiramycin Rovamycine Mouth infections
Monobactams
Aztreonam Azactam Gram-negative bacteria Same mode of
action as

28. 28
other beta-
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell
walls.
Nitrofurans
Furazolidone Furoxone
Bacterial
or protozoal diarrheaor e
nteritis
Nitrofurantoin(Bs)
Macrodantin,Ma
crobid
Urinary tract infections
Oxazolidinones(Bs)
Linezolid Zyvox VRSA
Thromboc
ytopenia
Peripheral
neuropathy
Serotonin
Syndrome
Protein synthesis
inhibitor;
prevents the
initiation step
Posizolid
Phase II clinical
trials
Radezolid Phase II clinical

29. 29
trials
Torezolid
Phase II clinical
trials
Penicillins
Amoxicillin
Novamox,Amoxi
l
Wide range of infections;
penicillin used
forstreptococcal
infections,syphilis,
and Lyme disease
Gastrointe
stinal
upset and
diarrhea
Allergy
with
seriousana
phylactic
reactions
Brain and
kidney
damage
(rare)
Same mode of
action as
other beta-
lactam
antibiotics:
disrupt the
synthesis of
thepeptidoglyca
n layer of
bacterial cell
walls.
Ampicillin
Principen
(discontinued)
Azlocillin
Carbenicillin
Geocillin
(discontinued)
Cloxacillin
Tegopen
(discontinued)
Dicloxacillin
Dynapen
(discontinued)
Flucloxacillin
Floxapen(Sold to
European
generics Actavis
Group)
Mezlocillin
Mezlin
(discontinued)
Methicillin Staphcillin

30. 30
(discontinued)
Nafcillin
Unipen
(discontinued)
Oxacillin
Prostaphlin
(discontinued)
Penicillin G
Pentids
(discontinued)
Penicillin V
Veetids (Pen-
Vee-K)
(discontinued)
Piperacillin
Pipracil
(discontinued)
Penicillin G Pfizerpen
Temocillin
Negaban (UK)
(discontinued)
Ticarcillin
Ticar
(discontinued)
Penicillin combinations
Amoxicillin/clavul
anate
Augmentin
Both
Amoxicillin/clavulanate
and
Ampicillin/sulbactam are
effective against non-
The second
component
prevents
bacterialresistan
ce to the first

31. 31
recurrent acute Otitis
mediaOnly a few oral-
antibiotics active for skin
and soft tissue infections,
one of it is
Amoxicillin/clavulanate.
Not to be given to
children with less than
40 kilograms weight, for
children are heavier, the
dosage is same with
adult, twice daily
component
Ampicillin/sulbact
am
Unasyn
Piperacillin/tazoba
ctam
Zosyn
Ticarcillin/clavula
nate
Timentin
Polypeptides
Bacitracin
Eye, ear or bladder
infections; usually
applied directly to the
eye or inhaled into the
lungs; rarely given by
injection, although the
use of intravenous
colistin is experiencing a
Kidney and
nerve damage
(when given
by injection)
Inhibits isopreny
l pyrophosphate,
a molecule that
carries the
building blocks
of
thepeptidoglyca
n bacterialcell

32. 32
resurgence due to the
emergence of multi drug
resistant organisms.
wall outside of
the inner
membrane
Colistin Coly-Mycin-S Interact with the
Gram-
negative bacteria
l outer
membrane andcy
toplasmic
membrane,
displacing
bacterial
counterions,
which
destabilizes the
outer membrane.
Act like a
detergent against
the cytoplasmic
membrane,
which alters its
permeability.
Polymyxin B
and E are
bactericidal even
in an isosmotic
solution.
Polymyxin B
Quinolones/Fluoroquinolone

33. 33
Ciprofloxacin
Cipro,Ciproxin,
Ciprobay
Urinary tract
infections,bacterial
prostatitis, community-
acquiredpneumonia, bact
erial
diarrhea, mycoplasmal
infections, gonorrhea
Nausea (rare),
irreversible
damage
tocentral
nervous
system (uncom
mon),
tendinosis
(rare)
inhibit the
bacterial DNA
gyrase or
thetopoisomeras
e IV enzyme,
thereby
inhibiting DNA
replication and
transcription.
Enoxacin Penetrex
Gatifloxacin Tequin
Gemifloxacin Factive
Levofloxacin Levaquin
Lomefloxacin Maxaquin
Moxifloxacin Avelox
Nalidixic acid NegGram
Norfloxacin Noroxin
Ofloxacin
Floxin
(discontinued),
Ocuflox
Trovafloxacin Trovan Withdrawn
Grepafloxacin Raxar Withdrawn
Sparfloxacin Zagam Withdrawn
Temafloxacin Omniflox Withdrawn
Sulfonamides(Bs)
Mafenide Sulfamylon Urinary tract Nausea, Folate

34. 34
Sulfacetamide
Sulamyd, Bleph-
10
infections(except
sulfacetamide, used
for eye infections, and
mafenide and silver
sulfadiazine, used
topically forburns)
vomiting,
and
diarrhea
Allergy (in
cluding
skin
rashes)
Crystals in
urine
Kidney
failure
Decrease
in white
blood
cell count
Sensitivity
to sunlight
synthesisinhibiti
on. They
arecompetitive
inhibitors of the
enzymedihydrop
teroate
synthetase,
DHPS. DHPS
catalyses the
conversion of
PABA (para-
aminobenzoate)
todihydropteroat
e, a key step
in folate synthesi
s. Folate is
necessary for the
cell to
synthesizenuclei
c acids (nucleic
acids are
essential
building blocks
of DNAand RN
A), and in its
absence cells
cannot divide.
Sulfadiazine Micro-Sulfon
Silver sulfadiazine Silvadene
Sulfadimethoxine
Di-Methox,
Albon
Sulfamethizole Thiosulfil Forte
Sulfamethoxazole Gantanol
Sulfanilimide (arc
haic)
Sulfasalazine Azulfidine
Sulfisoxazole Gantrisin
Trimethoprim-
Sulfamethoxazole(
Co-trimoxazole)
(TMP-SMX)
Bactrim, Septra
Sulfonamidochrys
oidine(archaic)
Prontosil

35. 35
Tetracyclines(Bs)
Demeclocycline Declomycin
Syphilis, chlamydialinfec
tions, Lyme
disease,mycoplasmal
infections,
acnerickettsial infections,
*malaria*Note: Malaria
is caused by aprotist and
not a bacterium.
Gastrointe
stinal
upset
Sensitivity
to sunlight
Potential
toxicity to
mother
and fetus
during
pregnancy
Enamel
hypoplasia
(staining
of teeth;
potentially
permanent
)
transient
depression
of bone
growth
inhibiting the
binding
ofaminoacyl-
tRNA to
themRNA-
ribosome compl
ex. They do so
mainly by
binding to
the 30S
ribosomal
subunit in
themRNA
translationcompl
ex. But
Tetracycline
cannot be taken
together with all
dairy products,
aluminium, iron
and zinc
minerals.
Doxycycline Vibramycin
Minocycline Minocin
Oxytetracycline Terramycin
Tetracycline
Sumycin,Achro
mycin V,Steclin
Drugs against mycobacteria
Clofazimine Lamprene Antileprotic
Dapsone Avlosulfon Antileprotic

36. 36
Capreomycin Capastat Antituberculosis
Cycloserine Seromycin
Antituberculosis, urinary
tract infections
Ethambutol(Bs) Myambutol Antituberculosis
Ethionamide Trecator Antituberculosis
Inhibits peptide
synthesis
Isoniazid I.N.H. Antituberculosis
Pyrazinamide Aldinamide Antituberculosis
Rifampicin (Rifam
pin in US)
Rifadin,
Rimactane
mostly Gram-
positive andmycobacteria
Reddish-
orange sweat,
tears, and
urine
Binds to the β
subunit ofRNA
polymerase to
inhibit
transcription
Rifabutin Mycobutin
Mycobacterium
aviumcomplex
Rash,
discolored
urine, GI
symptoms
Rifapentine Priftin Antituberculosis
Streptomycin Antituberculosis
Neurotoxicity,
ototoxicity
As
other aminoglyc
osides
Others

37. 37
Arsphenamine Salvarsan
Spirochaetal infections
(obsolete)
Chloramphenicol(
Bs)
Chloromycetin
Meningitis, MRSA,
topical use, or for low-
cost internal treatment.
Historic: typhus,cholera.
Gram-negative,Gram-
positive, anaerobes
Rarely: aplasti
c anemia.
Inhibits bacterial
protein synthesis
by binding to the
50S subunit of
the ribosome
Fosfomycin
Monurol,
Monuril
Acute cystitis in women
This antibiotic
is not
recommended
for children
and 75 up of
age
Inactivates enolp
yruvyl
transferase,
thereby
blocking cell
wallsynthesis
Fusidic acid Fucidin
Metronidazole Flagyl
Infections caused
byanaerobic bacteria;
alsoamoebiasis, trichomo
niasis,giardiasis
Discolored
urine,headache
, metallic
taste, nausea; a
lcoholis
contraindicate
d
Produces
toxic free
radicals that
disrupt DNA
and proteins.
This non-
specific
mechanism is
responsible for
its activity
against a variety
of bacteria,

38. 38
amoebae, and
protozoa.
Mupirocin Bactroban
Ointment for impetigo, c
reamfor infected cuts
Inhibits
isoleucine t-
RNA synthetase
(IleRS) causing
inhibition of
protein synthesis
Platensimycin
Quinupristin/Dalfo
pristin
Synercid
Thiamphenicol
Gram-negative, Gram-
positive, anaerobes.
Widely used in
veterinary medicine.
Rash. Lacks
known anemic
side-effects.
A
chloramphenicol
analog. May
inhibit bacterial
protein synthesis
by binding to the
50S subunit of
the ribosome
Tigecycline(Bs) Tigacyl
Slowly Intravenous.
Indicated for
complicated skin/skin
structure infections, soft
tissues infections and
complicated intra-
abdominal infections.
Effective for gram
Teeth
discoloration
and same side
effects
as Tetracycline
. Not to be
given for
children and
Similar structure
with
tetracycline, but
5 times stronger,
big volume
distribution and
long half-time in

39. 39
positive and negative and
also anaerob antibiotics,
against multi-resistant
antibiotics bacteries such
asStaphylococcus
aureus(MRSA)
and Acinetobacter
baumannii, but not
effective for
Pseudomonas spp and
Proteus spp
pregnant or
lactate women.
Relatively safe
and no need
dose adjusted
when be given
for mild to
moderate liver
function or
renal patients
the body
Tinidazole
Tindamax
Fasigyn
Protozoal infections
Upset
stomach, bitter
taste, and
itchiness
Trimethoprim(Bs)
Proloprim,
Trimpex
Urinary tract infections

40. 40
3.2Antibiotic use in livestock
It is the use of antibiotics for any purpose in the husbandry of livestock, which includes
not only the treatment or prophylaxis of infection but also the use of subtherapeutic doses
in animal feed to promote growth and improve feed efficiency in contemporary intensive animal
farming. Antimicrobials (including antibiotics and antifungals) and other drugs are used
byveterinarians and livestock owners to increase the size of livestock, poultry, and other farmed
animals. The use of some drugs is banned in some countries due to food contamination or
concern about increasing antibiotic resistance and what some consider antibiotic misuse. Other
drugs may be used only under strict limits, and some organizations and authorities seek to further
restrict the use of some or all drugs in animals. Other authorities, such as the World Organization
for Animal Health, say that concerns for bacterial resistance in humans is overblown and
restricting the availability of medicine is detrimental to animal health and the economical
production of food.
 History of the practice
In 1910 in the United States, a meat shortage resulted in protests and boycotts. After this
and other shortages, the public demanded government research into stabilization of food
supplies. Since the 1900s, livestock production on United States farms has had to rear larger
quantities of animals over a short period of time to meet new consumer demands. Along with the
new large animal densities came the threat of disease, therefore requiring a greater disease
control of these animals. In 1950, a group of United States scientists found that adding
antibiotics to animal feed increases the growth rate of livestock. American Cyanamid published
research establishing the practice.
By 2001 this practice had grown so much that a report by the Union of Concerned
Scientists found that nearly 90% of the total use of antimicrobials in the United States was for
non-therapeutic purposes in agricultural production.

41. 41
3.3Drugs and growth stimulation
Certain antibiotics, when given in low, sub-therapeutic doses, are known to improve feed
conversion efficiency (more output, such as muscle or milk, for a given amount of feed) and/or
may promote greater growth, most likely by affecting gut flora.
Antibiotic Growth Promoters used in Livestock Production
drug class effect
Bambermycin
increase feed conversion ratio; growth promotion in poultry and
cattle
Lasalocid Ionophore increase feed conversion ratio
Monensin Ionophore
increase feed conversion ratio; increase weight gain in cattle and
sheep
Salinomycin Ionophore increase feed conversion ratio; increase weight gain
Virginiamycin peptide promotes growth of poultry
Bacitracin peptide promotes growth of poultry

42. 42
3.4Use in different livestock
1. In swine production
The use of antibiotics to increase the growth of pigs is most studied of all livestock. This
use for growth rather than disease prevention is referred to as subtherapeutic antibiotic use.
Studies have shown that administering low doses of antibiotics in livestock feed improves
growth rate, reduces mortality and morbidity, and improves reproductive performance. It is
estimated that over one-half of the antibiotics produced and sold in the United States is used as a
feed additive. Although it is still not completely understood why and how antibiotics increase the
growth rate of pigs, possibilities include metabolic effects, disease control effects, and nutritional
effects. While subtherapeutic use has many benefits for raising swine, there is growing concern
that this practice leads to increased antibiotic resistance in bacteria. Antibiotic resistance occurs
when bacteria are resistant to one or more microbial agents that are usually used to treat
infection. There are three stages in the possible emergence and continuation of antibiotic
resistance: genetic change, antibiotic selection, and spread of antibiotic resistance.
2. In production of other livestock
Regulatory context
The use of drugs in food animals is regulated in nearly all countries. Historically, this has
been to prevent alteration or contamination of meat, milk, eggs and other products with toxins
that are harmful to humans. Treating a sick animal with drugs may lead to some of those drugs
remaining in the animal when it is slaughtered or milked. Scientific experiments provide data
that shows how long a drug is present in the body of an animal and what the animal's body does
to the drug. Of particular concern are drugs that may be passed into milk or eggs. By the use of
'drug withdrawal periods' before slaughter or the use of milk or eggs from treated animals,
veterinarians and animal owners ensure that the meat, milk and eggs is free of contamination.
These restrictions include not only poisons or drugs (such as penicillin) which may result
in allergic reactions but also contaminants which may cause cancer. It is illegal in the USA to
administer drugs or feed substances to animals if they have been shown to cause cancer.
One of the main restrictions is the amount that is administered to animals in the industry.
These drugs should be administered to healthy livestock at a low concentration of 200 g per ton

43. 43
of feed. The amount distributed is also altered throughout the lifespan of livestock in order to
meet specific growth needs.
Legality of the use of specific drugs in animal medicine varies according to location.Just
as in human medicine, some drugs are available over the counter and others are restricted to use
only on the prescription of aveterinary physician. In the USA, the Food and Drug
Administration (FDA) requires specific labels on all drugs, giving directions on the use of the
drug. For animals, this includes the species, dose, reason for giving the drug (indication) and the
required withdrawal period, if any. Federal law requires laypersons to use drugs only in the
manner listed. Veterinarians who have examined an animal or a herd of animals may issue a
replacement label, giving new directions, based on their medical knowledge. It is illegal in the
USA for any layperson to administer any drug to a food animal in a way not specific to the drug
label. Over-the-counter drugs which may be used by laypersons include anti-parasite drugs
(including fly sprays) and antimicrobials. These drugs can be applied as sprays, creams,
injections, oral pills or fluids, or as a feed additive, depending on the drug and the label.
In December 2013, the FDA updated its regulations to try to begin reducing use of
antibiotics for growth enhancement. Significantlobbying comes from all directions, from those
against tighter regulation to those who complain it doesn't go far enough.
Nearly all hormones and painkillers are illegal for laypersons to use in food animals.
Additionally, there are very few drugs labelled for use in laying hens, ducks, goats, meat rabbits,
or other minor species.If a layperson gives a drug to a food animal, they are responsible for
ensuring that an adequate withdrawal period is allowed to ensure that the meat or milk is not
contaminated.
For drugs that can not be legally given by lay persons, or if the animal or herd does not
respond to treatment, a veterinary physician may prescribe a different drug or one at a different
dose than is on the label. The veterinarian will also give directions as to the appropriate
withdrawal period.

44. 44
Chapter-4
Production of antibiotics
With advances in medicinal chemistry, most modern antibacterials
are semisynthetic modifications of various natural compounds. These include, for example,
the beta-lactam antibiotics, which include the penicillins (produced by fungi in the
genus Penicillium), thecephalosporins, and the carbapenems. Compounds that are still isolated
from living organisms are the aminoglycosides, whereas other antibacterials—for example,
the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical
synthesis. In accordance with this, many antibacterial compounds are classified on the basis of
chemical/biosynthetic origin into natural, semisynthetic, and synthetic. Another classification
system is based on biological activity; in this classification, antibacterials are divided into two
broad groups according to their biological effect on microorganisms: Bactericidal agents kill
bacteria, andbacteriostatic agents slow down or stall bacterial growth.Many antibacterial
compounds are relatively small moleculeswith a molecular weight of less than 2000 atomic mass
units.
Since the first pioneering efforts of Florey and Chain in 1939, the importance of
antibiotics, including antibacterials, to medicine has led to intense research into producing
antibacterials at large scales. Following screening of antibacterials against a wide range of
bacteria, production of the active compounds is carried out using fermentation, usually in
strongly aerobic conditions.
The production of antibiotics has been widespread since the pioneering efforts
of Florey and Chain in 1938. The importance ofantibiotics to medicine has led to much research
into their discovery and production.

45. 45
4.1 Identifying useful antibiotics
Despite the wide variety of known antibiotics, less than 1% of antimicrobial agents have
medical or commercial value. For example, whereas penicillin has a high therapeutic index as it
does not generally affect human cells, this is not so for many antibiotics. Other antibiotics simply
lack advantage over those already in use, or have no other practical applications.
Useful antibiotics are often discovered using a screening process. To conduct such a screen,
isolates of many different microorganisms are cultured and then tested for production
ofdiffusible products that inhibit the growth of test organisms. Most antibiotics identified in such
a screen are already known and must therefore be disregarded. The remainder must be tested for
their selective toxicities and therapeutic activities, and the best candidates can be examined and
possibly modified.
A more modern version of this approach is a rational design program. This involves
screening directed towards finding new natural products that inhibit a specific target, such as
an enzyme only found in the target pathogen, rather than tests to show general inhibition of a
culture.
4.2Industrial production techniques
Antibiotics are produced industrially by a process of fermentation, where the source
microorganism is grown in large containers (100,000–150,000 liters or more) containing a
liquid growth medium. Oxygen concentration, temperature, pH and nutrient levels must be
optimal, and are closely monitored and adjusted if necessary. As antibiotics are secondary
metabolites, the population size must be controlled very carefully to ensure that maximum yield
is obtained before the cells die. Once the process is complete, the antibiotic must be extracted
and purified to a crystalline product. This is simpler to achieve if the antibiotic is soluble
in organic solvent. Otherwise it must first be removed by ion exchange, adsorption or chemical
precipitation.
4.3Strains used for production
Microorganisms used in fermentation are rarely identical to the wild type. This is because
species are often genetically modified to yield the maximum amounts of antibiotics. Mutation is

46. 46
often used, and is encouraged by introducing mutagens such as ultraviolet radiation, x-rays or
certain chemicals. Selection and further reproduction of the higher yielding strains over many
generations can raise yields by 20-fold or more. Another technique used to increase yields
is gene amplification, where copies of genes coding for enzymes involved in the antibiotic
production can be inserted back into a cell, via vectors such as plasmids. This process must be
closely linked with retesting of antibiotic production.

47. 47
Chapter-5
Adminstration
Oral antibiotics are taken by mouth, whereas intravenous administration may be used in more
serious cases, such as deep-seated systemic infections. Antibiotics may also sometimes be
administered topically, as with eye drops or ointments.
 The topical antibiotics are:
1. Erythromycin
2. Clindamycin
3. Gentamycin
4. Tetracycline
5. Meclocycline
6. (Sodium) sulfacetamide
 While topical medications that act as Comedolytics as well as antibiotics are:
1. Benzoyl peroxide
2. Azelaic acid
5.1The topical antibiotics
1. Erythromycin
Erythromycin is an antibiotic useful for the treatment of a number
of bacterial infections. It is in the macrolide class and has an antimicrobial spectrum similar
to or slightly wider than that of penicillin, and is often prescribed for people who have
an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical
organisms, includingMycoplasma and Legionella. It was first marketed by Eli Lilly and
Company, and it is today commonly known as erythromycin ethylsuccinate (EES), a
commonly administered ester prodrug. It is commonly applied after delivery to the eyes of

48. 48
newborns to preventneonatal conjunctivitis. It is used as an alternative treatment to treat
sexually transmitted diseases.
Fig: Erythromycin structure
Systematic (IUPAC) name
(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-
{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-
14-ethyl-7,12,13-trihydroxy-4-{[(2R,4R,5S,6S)-
5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-
3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione
Erythromycin improves gastric emptying and symptoms from delayed gastric emptying,
yet it is used in an off-label basis. Intravenous (IV) erythromycin Is sometimes administered
when IV prokinetic therapy is needed in hospitalized patients. Oral treatment with erythromycin
improves gastric emptying, but has limited long-term efficacy.
In structure, this macrocyclic compound contains a 14-membered lactone ring with 10
asymmetric centers and two sugars (L-cladinose and D-desosamine), making it a compound very
difficult to produce by synthetic methods. Erythromycin is produced from a strain of the
actinomycete Saccharopolyspora erythraea.

49. 49
It is on the World Health Organization's List of Essential Medicines, a list of the most important
medications needed in a basic health system.
 Erythromycin History
Dr. Abelardo B. Aguilar, a Filipino scientist, sent some soil samples to his employer Eli
Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate erythromycin
from the metabolic products of a strain of Streptomyces erythreus(designation changed to
"Saccharopolyspora erythraea") found in the samples.
Lilly filed for patent protection of the compound and U.S. patent 2,653,899 was granted in
1953. The product was launched commercially in 1952 under the brand name Ilosone(after
the Philippine region of Iloilo where it was originally collected). Erythromycin was formerly also
called Ilotycin.
In 1981, Nobel laureate (1965 in chemistry) and professor of chemistry at Harvard
University (Cambridge, MA) Robert B. Woodward (posthumously), along with a large number
of members from his research group, reported the first stereocontrolled asymmetric chemical
synthesis of erythromycin A. The antibiotic clarithromycin was invented by scientists at the
Japanese drug companyTaisho Pharmaceutical in the 1970s as a result of their efforts to
overcome the acid instability of erythromycin.Scientists at Chugai Pharmaceuticals discovered
an erythromycin-derived motilin agonist called mitemcinal that is believed to have
strong prokinetic properties (similar to erythromycin) but lacking antibiotic properties.
Erythromycin is commonly used off-labelfor gastric motility indications such as gastroparesis. If
mitemcinal can be shown to be an effective a prokinetic agent, it would represent a significant
advance in the gastrointestinal field, as treatment with this drug would not carry the risk of
unintentional selection for antibiotic-resistant bacteria.
 Adverse effects
Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are
very common because erythromycin is amotilin agonist. Because of this, erythromycin tends not
to be prescribed as a first-line drug. However, it may be useful in treatinggastroparesis due to this
promotility effect. Intravenous erythromycin may also be used in endoscopy as an adjunct to
clear gastriccontents.More serious side effects include arrhythmia with prolonged QT

50. 50
intervals including torsades de pointes, and reversible deafness. Allergic reactions range
from urticaria to anaphylaxis. Cholestasis, Stevens–Johnson syndrome, and toxic epidermal
necrolysis are some other rare side effects that may occur.
Studies have shown evidence both for and against the association of pyloric stenosis and
exposure to erythromycin prenatally and postnatally. Exposure to erythromycin (especially long
courses at antimicrobial doses, and also through breastfeeding) has been linked to an increased
probability of pyloric stenosis in young infants. Erythromycin used for feeding intolerance in
young infants has not been associated with hypertrophic pyloric stenosis.
Erythromycin estolate has been associated with reversible hepatotoxicity in pregnant
women in the form of elevated serum glutamic-oxaloacetic transaminase and is not
recommended during pregnancy. Some evidence suggests similar hepatotoxicity in other
populations. It can also affect the central nervous system, causing psychotic reactions,
nightmares and night sweats.
It may also alter the effectiveness of combined oral contraceptive pills because of its
effect on the gut flora. Erythromycin is an inhibitor of the cytochrome P450 system, which
means it can have a rapid effect on levels of other drugs metabolised by this system, e.g.,
warfarin.
 Synthesis
Over the three decades after the discovery of erythromycin A and its activity as an
antimicrobial, many attempts were made to synthesize it in the laboratory. However, the
presence of 10 stereospecific carbons and several points of distinct substitution has made the
total synthesis of erythromycin A a formidable task. Complete syntheses of erythromycins’
related structures and precursors such as 6-deoxyerythronolide B have been accomplished,
giving way to possible syntheses of different erythromycins and other macrolide
antimicrobials. However, Woodward did successfully complete the synthesis of erythromycin
A. This total synthesis begins with (7) and (8). After being coupled, the resulting structure is
subjected to a series of reactions, including hydrolysis and stereospecific aldolization. The
resulting pure enone is then converted to the desired (9) through a series of reduction and

51. 51
oxidation reactions. The dithiadecalin product (9) is then converted to both a ketone (10) and an
aldehyde (11)
 Available forms
Erythromycin is available in enteric-coated tablets, slow-release capsules, oral suspensions,
ophthalmic solutions, ointments, gels, Enteric-coated Capsules Non Enteric-coated tablets Non
Enteric-coated capsules and injections.
Fig:Enteric-coated erythomycin capsule from Abbott Labs
 The following erythromycin combinations are available for oral dosage:
erythromycin base (capsules, tablets)
erythromycin estolate (capsules, oral suspension, tablets), contraindicated during pregnancy
erythromycin ethylsuccinate (oral suspension, tablets)
erythromycin stearate (oral suspension, tablets)
 For injection the available combinations are:
erythromycin gluceptate
erythromycin lactobionate
Brand names include Robimycin, E-Mycin, E.E.S. Granules, E.E.S.-200, E.E.S.-400,
E.E.S.-400 Filmtab, Erymax, Ery-Tab, Eryc, Ranbaxy, Erypar, EryPed, Eryped 200, Eryped 400,
Erythrocin Stearate Filmtab, Erythrocot, E-Base, Erythroped, Ilosone, MY-E, Pediamycin,
Zineryt, Abboticin, Abboticin-ES, Erycin, PCE Dispertab, Stiemycine, Acnasol, and Tiloryth.

52. 52
 Composition
Standard-grade erythromycin is primarily composed of four related compounds known as
erythromycins A, B, C, and D. Each of these compounds can be present in varying amounts and
can differ by lot. Erythromycin A has been found to have the most antibacterial activity,
followed by erythromycin B. Erythromycins C and D are about half as active as erythromycin
A. Some of these related compounds have been purified and can be studied and researched
individually.
 Spectrum of susceptibility
Erythromycin can be used to treat bacteria responsible for causing infections of the skin
and upper respiratory tract, includingStreptococcus, Staphylococcus, and Haemophilus genera.
The following represents MIC susceptibility data for a few medically significant bacteria:
Haemophilus influenzae: 0.015 to 256 μg/ml
Staphylococcus aureus: 0.023 to 1024 μg/ml
Streptococcus pyogenes: 0.004 to 256 μg/ml
 Mechanism of action
Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at
higher concentrations, but the mechanism is not fully understood. By binding to the 50s subunit
of the bacterial 70s rRNA complex, protein synthesis and subsequent structure and function
processes critical for life or replication are inhibited. Erythromycin interferes with aminoacyl
translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to
the P site of the rRNA complex. Without this translocation, the A site remains occupied, thus the
addition of an incoming tRNA and its attached amino acid to the nascent polypeptide chain is
inhibited. This interferes with the production of functionally useful proteins, which is the basis of
this antimicrobial action.
 Pharmacokinetics
Erythromycin is easily inactivated by gastric acid; therefore, all orally administered
formulations are given as either enteric-coated or more-stable salts or esters, such as

53. 53
erythromycin ethylsuccinate. Erythromycin is very rapidly absorbed, and diffuses into most
tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively
transported to the site of infection, where, during active phagocytosis, large concentrations of
erythromycin are released.
 Metabolism
Most of erythromycin is metabolised by demethylation in the liver by the hepatic enzyme
CYP3A4. Its main elimination route is in thebile with little renal excretion, 2%-15% unchanged
drug. Erythromycin's elimination half-life ranges between 1.5 and 2.0 hours and is between 5 and
6 hours in patients with end-stage renal disease. Erythromycin levels peak in the serum 4 hours
after dosing; ethylsuccinate peaks 0.5-2.5 hours after dosing, but can be delayed if digested with
food.
Erythromycin crosses the placenta and enters breast milk. The American Association of
Pediatrics determined erythromycin is safe to take while breastfeeding. Absorption in pregnant
patients has been shown to be variable, frequently resulting in levels lower than in nonpregnant
patients.
 Interactions
Erythromycin is metabolized by enzymes of the cytochrome P450 system, in particular,
by isozymes of the CYP3A superfamily, CYP3A. The activity of the CYP3A enzymes can be
induced or inhibited by certain drugs (e.g. dexamethasone) which can cause it to affect
the metabolism of many different drugs, e.g. erythromycin. If other CYP3A substrates — drugs
that are broken down by CYP3A — such as simvastatin (Zocor), lovastatin (Mevacor),
or atorvastatin (Lipitor)—are taken concomitantly with erythromycin, levels of the substrates
increase, often causing adverse effects.
A noted drug interaction involves erythromycin and simvastatin, resulting in increased
simvastatin levels and the potential for rhabdomyolysis. Another group of CYP3A4 substrates
are drugs used formigraine such as ergotamine and dihydroergotamine; their adverse effects may
be more pronounced if erythromycin is associated. Earlier case reports on sudden death
prompted a study on a large cohort that confirmed a link between erythromycin, ventricular

54. 54
tachycardia, and sudden cardiac death in patients also taking drugs that prolong the metabolism
of erythromycin (like verapamil ordiltiazem) by interfering with CYP3A4.
Hence, erythromycin should not be administered to people using these drugs, or drugs
that also prolong the QT interval. Other examples include terfenadine (Seldane, Seldane-
D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the
QT time) and pimozide (Orap). Theophylline, which is used mostly in asthma, is also
contraindicated.
Erythromycin may affect neuromuscular transmission by acting presynaptically, so may
produce or worsen symptoms of myasthenia gravis in patients with pre-existing postsynaptic
defects. Exacerbations of myasthenia gravis have also been reported with the use of
telithromycin and azithromycin. Erythromycin is not recommended when using clindamycin-
containing products, even topical products such as Duac or BenzaClin. In general, the
simultaneous use of two different erythromycin derivatives (such as clindamycin
and Mitemcinal) should be avoided as drugs in this macrolide family possess a common
mechanism of action .Erythromycin and Doxycycline can have a synergistic effect when
combined and kill bacteria (E. coli) with a higher potency than the sum of the two drugs
together. However, this synergistic relationship is only temporary. After approximately 72 hours,
the relationship shifts to become antagonistic, whereby a 50/50 combination of the two drugs
kills less bacteria than if the two drugs were administered separately.
 Erythromycin-derived compounds
Ansamycin
Azithromycin (Zithromax, Zitromax, Sumamed)
Carbomycin
Cethromycin
Clarithromycin (Biaxin)
Dirithromycin (Dynabac)
Mitemcinal
Oleandomycin
Roxithromycin (Rulid, Surlid, Roxid)

55. 55
Spiramycin
Telithromycin
Tylosin (Tylocine)
2. Clindamycin
Fig: Clindamycin structure
Systematic (IUPAC) name
methyl 7-chloro-6,7,8-trideoxy-6-{[(4R)-1-methyl-4-propyl-L-prolyl]amino}-1-thio-L-threo-α-
D-galacto-octopyranoside
 Clindamycin is an antibiotic of the lincosamide class, which blocks the ribosomes of
microorganisms. It is usually used to treat infections withanaerobic bacteria, but can also be
used to treat protozoal diseases, such as malaria. It is a common topical treatment
for acne and can be useful against some methicillin-resistantStaphylococcus aureus (MRSA)
infections. The most severe common adverse effect of clindamycin is Clostridium difficile-
associateddiarrhea (the most frequent cause of pseudomembranous colitis). Although

56. 56
this side effectoccurs with almost all antibiotics, including beta-lactam antibiotics, it is
classically linked to clindamycin use.
 Clindamycin is marketed as generic and under trade names including Cleocin HCl-
(Pfizer), Dalacin, Lincocin (Bangladesh), and Dalacin, Clindacin. Combination products
include Duac, BenzaClin, Clindoxyl and Acanya (in combination with benzoyl peroxide),
and Ziana (with tretinoin). It is on the World Health Organization's List of Essential
Medicines, a list of the most important medication needed in a basic health system.
 Medical uses
Clindamycin is used primarily to treat anaerobic infections caused by
susceptibleanaerobic bacteria, including dental infections, and infections of the respiratory tract,
skin, and soft tissue, and peritonitis. In people with hypersensitivity to penicillins, clindamycin
may be used to treat infections caused by susceptible aerobic bacteria, as well. It is also used to
treat bone and joint infections, particularly those caused byStaphylococcus
aureus. Topical application of clindamycin phosphate can be used to treat mild to moderate acne.
 Acne
The use of clindamycin in conjunction with benzoyl peroxide is more effective in the
treatment of acne than the use of either product by itself. Clindamycin and adapalene in
combination are also more effective than either drug alone, although adverse effects are more
frequent.
 Susceptible bacteria
It is most effective against infections involving the following types of organisms:
Aerobic Gram-positive cocci,including some members of the Staphylococcus and
Streptococcus genera,but not enterococci.
Anaerobic, Gram-negative rod-shaped bacteria, including some Bacteroides,Fusobacterium,
and Prevotella, although resistance is increasing in Bacteroides fragilis.
Most aerobic Gram-negative bacteria (such as Pseudomonas, Legionella, Haemophilus
influenzae and Moraxella) are resistant to clindamycin, as are the facultative

57. 57
anaerobic Enterobacteriaceae. A notable exception is Capnocytophaga canimorsus, for which
clindamycin is a first-line drug of choice.
 The following represents MIC susceptibility data for a few medically significant pathogens.
Staphylococcus aureus: 0.016 μg/ml - >256 μg/ml
Streptococcus pneumoniae: 0.002 μg/ml - >256 μg/ml
Streptococcus pyogenes: <0.015 μg/ml - >64 μg/ml
 D-Test
When testing a Gram-positive culture for sensitivity to clindamycin, it is common to
perform a "D-Test" to determine if there is amacrolide-resistant subpopulation
of bacteria present. This test is necessary because some bacteria express a phenotype known as
MLSB, in which susceptibility tests will indicate the bacteria are susceptible to clindamycin,
but in vitro the pathogen displays inducibleresistance.To perform a D-test, an agar plate is
inoculated with the bacteria in question and two drug-impregnated disks (one with erythromycin,
one with clindamycin) are placed 15–20 mm apart on the plate. If the area of inhibition around
the clindamycin disk is "D" shaped, the test result is positive and clindamycin should not be used
due to the possibility of resistant pathogens and therapy failure. If the area of inhibition around
the clindamycin disk is circular, the test result is negative and clindamycin can be used.
 Malaria
Given with chloroquine or quinine, clindamycin is effective and well tolerated in
treating Plasmodium falciparum malaria; the latter combination is particularly useful for
children, and is the treatment of choice for pregnant women who become infected in areas
whereresistance to chloroquine is common. Clindamycin should not be used as an antimalarial
by itself, although it appears to be very effective as such, because of its slow action. Patient-
derived isolates of Plasmodium falciparum from the Peruvian Amazon have been reported to be
resistant to clindamycin as evidenced by in vitro drug susceptibility testing.
 Other
Clindamycin may be useful in skin and soft tissue infections caused by methicillin-
resistant Staphylococcus aureus (MRSA); many strains of MRSA are still susceptible to

58. 58
clindamycin; however, in the United States spreading from the West Coast eastwards, MRSA is
becoming increasingly resistant.
Clindamycin is used in cases of suspected toxic shock syndrome, often in combination
with a bactericidal agent such asvancomycin. The rationale for this approach is a presumed
synergy between vancomycin, which causes the death of the bacteria bybreakdown of the cell
membrane, and clindamycin, which is a powerful inhibitor of toxin synthesis. Both in
vitro and in vivo studies have shown clindamycin reduces the production of exotoxins by
staphylococci; it may also induce changes in the surface structure of bacteria that make them
more sensitive to immune system attack (opsonization and phagocytosis). Clindamycin has been
proven to decrease the risk of premature births in women diagnosed with bacterial
vaginosis during early pregnancy to about a third of the risk of untreated women.
The combination of clindamycin and quinine is the standard treatment for
severe babesiosis. Clindamycin may also be used to treat toxoplasmosis, and, in combination
with primaquine, is effective in treating mild to moderate Pneumocystis jirovecii pneumonia.
 Adverse effects
Common adverse drug reactions associated with systemic clindamycin therapy found in
over 1% of people — include: diarrhea,pseudomembranous colitis , nausea , vomiting
, abdominal pain or cramps and/or rash. High doses (both intravenous and oral) may cause
a metallic taste. Common adverse drug reactions associated with topical formulations - found in
over 10% of people - include: dryness, burning, itching, scaliness, or peeling of skin (lotion,
solution) ; erythema (foam, lotion, solution); oiliness (gel, lotion). Additional side effects
include contact dermatitis. Common side effects - found in over 10% of people - in vaginal
applications include fungal infection.
Pseudomembranous colitis is a potentially lethal condition commonly associated with
clindamycin, but which occurs with other antibiotics, as well. Overgrowth of Clostridium
difficile, which is inherently resistant to clindamycin, results in the production of a toxin that
causes a range of adverse effects, from diarrhea to colitis and toxic megacolon. Rarely — in less
than 0.1% of patients — clindamycin therapy has been associated with anaphylaxis,

59. 59
blood dyscrasias, polyarthritis,jaundice, raised liver enzyme levels, renal dysfunction, cardiac
arrest, and/or hepatotoxicity.
 Chemistry
Clindamycin is a semisynthetic derivative of lincomycin, a natural antibiotic produced by
the actinobacterium Streptomyces lincolnensis. It is obtained by 7(S)-chloro-substitution of the
7(R)-hydroxyl group of lincomycin. The synthesis of clindamycin was first announced by BJ
Magerlein, RD Birkenmeyer, and F Kagan on the fifth Interscience Conference on Antimicrobial
Agents and Chemotherapy (ICAAC) in 1966. It has been on the market since 1968.
 Mechanism of action
Clindamycin has a primarily bacteriostatic effect. It is a bacterial protein synthesis
inhibitor by inhibiting ribosomal translocation, in a similar way to macrolides. It does so by
binding to the 50S rRNA of the large bacterial ribosome subunit. The structures of the complexes
between several antibiotics (including clindamycin) and a Deinococcus radiodurans ribosome
have been solved by X-ray crystallography by a team from the Max Planck Working Groups for
Structural Molecular Biology, and published in the journal Nature.
 Interactions
Clindamycin may prolong the effects of neuromuscular-blocking drugs, such
as succinylcholine and vecuronium. Its similarity to the mechanism of action
of macrolides and chloramphenicol means they should not be given simultaneously, as this
causes antagonism and possible cross-resistance.
 Available forms
Clindamycin preparations for oral administration include capsules (containing
clindamycin hydrochloride) and oral suspensions (containing clindamycin palmitate
hydrochloride) . Oral suspension is not favored for administration of clindamycin to children,
due to its extremely foul taste and odor. Clindamycin is formulated in a vaginal cream and
as vaginal ovules for treatment of bacterial vaginosis. It is also available for topical
administration in gel form, as a lotion, and in a foam delivery system (each containing

60. 60
clindamycin phosphate) and a solution in ethanol (containing clindamycin hydrochloride) and is
used primarily as a prescription acne treatment.
Several combination acne treatments containing clindamycin are also marketed, such as
single-product formulations of clindamycin with benzoyl peroxide—sold as BenzaClin (Sanofi-
Aventis), Duac (a gel form made by Stiefel), and Acanya, among other trade names—and, in the
United States, a combination of clindamycin and tretinoin, sold as Ziana. In India, vaginal
suppositories containing clindamycin in combination with clotrimazole are manufactured by
Olive Health Care and sold as Clinsup-V. In Egypt, vaginal cream containing clindamycin
produced by Biopharmgroup sold as Vagiclind indicated for vaginosis.
Clindamycin is available as a generic drug, for both systemic (oral and intravenous) and
topical use (The exception is the vaginal suppository, which is not available as a generic in the
USA).
 Veterinary use
The veterinary uses of clindamycin are quite similar to its human indications, and include
treatment of osteomyelitis, skin infections, and toxoplasmosis, for which it is the preferred drug
in dogs and cats. Toxoplasmosis rarely causes symptoms in cats, but can do so in very young
or immunocompromised kittens and cats.
3. Gentamicin
Gentamicin is an aminoglycoside antibiotic composed of a mixture of related gentamicin
components and fractions and is used to treat many types of bacterial infections, particularly
those caused by Gram-negativeorganisms. However, gentamicin is not used for Neisseria
gonorrhoeae,Neisseria meningitidis, or Legionella pneumophila. Gentamicin is
alsoototoxic and nephrotoxic, with this toxicity remaining a major problem in clinical use. It is
synthesized by Micromonospora, a genus of Gram-positive bacteriawidely present in the
environment (water and soil). To highlight their specific biological origins, gentamicin and other
related antibiotics produced by this genus generally have their spellings ending in ~micin and not
in ~mycin. Gentamicin is a bactericidal antibiotic that works by binding the 30S subunit of the
bacterial ribosome, interrupting protein synthesis.

61. 61
Like all aminoglycosides, when gentamicin is given orally, it is not systemically active. This
is because it is not absorbed to any appreciable extent from the small intestine. It is
administered intravenously,intramuscularly or topically to treat infections. It appears to be
completely eliminated unchanged in the urine. Urine must be collected for many days to recover
all of a given dose because the drug binds avidly to certain tissues.E. coli has shown some
resistance to gentamicin, despite being Gram-negative. Reluctance to use gentamicin for
empirical therapy has led to increased use of alternative broad-spectrum antibiotics, which some
experts suggest has led to the prevalence of antibiotic-resistant bacterial infections by MRSA and
other so-called "superbugs".
Fig: Gentamicin structure
Systematic (IUPAC) name
(3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4,6-
diamino-3-{[(2R,3R,6S)-
3-amino-6-[(1R)-
1-(methylamino)ethyl]oxan-2-yl]oxy}-
2-hydroxycyclohexyl]oxy}-5-methyl-
4-(methylamino)oxane-3,5-diol

62. 62
Gentamicin is one of the few heat-stable antibiotics that remain active even
after autoclaving, which makes it particularly useful in the preparation of some microbiological
growth media. It is used during orthopaedic surgery when high temperatures are required for the
setting of cements (e.g. hip replacements).
It is on the World Health Organization's List of Essential Medicines, a list of the most
important medication needed in a basic health system.
 Medical uses
Active against a wide range of human bacterial infections, mostly Gram-negative bacteria
including Pseudomonas, Proteus, Serratia, and the Gram-positive Staphylococcus. Gentamicin is
not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial
infections (because of the risk of the patient going into shock from lipid Aendotoxin found in
certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis, its relatives,
and Francisella tularensis (the organism responsible for tularemia seen often in hunters and/or
trappers). Some Enterobacteriaceae, Pseudomonas spp., enterococci,Staphylococcus aureus and
other staphylococci are resistant to gentamicin sulfate, to varying degrees.
 Optimal use in neonates
In neonates, evidence suggests that the use of large-dose, extended interval genta
regimens are more likely to achieve optimum peak and trough concentration when compared to
the traditional multiple daily dose regimens. In addition, the adjustment of dose and dosage
interval according to gestational age (GA) and birth weight is found to be suitable for preterm
neonates . Based on these rationales, several neonatal genta dosing regimens have been
proposed. However, there is a wide variety among these protocols (Darmstadt et al., 2008).
There is evidence of a relationship between serum genta levels, efficacy and incidence of toxic
events. Available data on the use of genta in neonates suggested that extended dosing intervals
and higher dose >= 4 mg/ kg confer favorable pharmacokinetic profile (high peak & low trough
level). This provides the basis for potential enhancement of therapeutic efficacy and reduces
toxicity.

63. 63
 Side effects
Aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their
relative effects on hearing versus balance. Gentamicin is a vestibulotoxin, and can cause
permanent loss of equilibrioception, caused by damage to the vestibular apparatus of the inner
ear, usually if taken at high doses or for prolonged periods of time, but there are well
documented cases in which gentamicin completely destroyed the vestibular apparatus after three
to five days. A small number of affected individuals have a normally harmless mutation in
their mitochondrial DNA encoding the 12S ribosomal RNA (m.1555 A>G), that allows the
gentamicin to affect their cells. The cells of the ear are particularly sensitive to this, sometimes
causing complete hearing loss. However, gentamicin is sometimes used intentionally for this
purpose in severe Ménière's disease, to disable the vestibular apparatus. These side effects are
most common when the drug is administered via drops directly to the ear.
Side effects of gentamicin toxicity vary from patient to patient. Side effects may become
apparent shortly after or up to months after gentamicin is administered.
 Symptoms of gentamicin toxicity include:
Balance difficulty
Bouncing, unsteady vision
Ringing in the ears (tinnitus)
Difficulty multi-tasking, particularly when standing
 Gentamicin is nephrotoxic. Risk factors for aminoglycoside nephrotoxicity include
patient factors such as:
increased age
reduced renal function
pregnancy
hypothyroidism
hepatic dysfunction
volume depletion
metabolic acidosis

64. 64
concurrent use of other drugs: vancomycin, NSAIDs, cisplatin, cyclosporin, cephalosporin,
diuretics
Concurrent use of iodinated contrast agents
Treatment factors can also affect toxicity. Important factors such as dose, frequency,
levels and duration of therapy can affect level of toxicity.Prevention of nephrotoxicity includes
judicouss use of IV fluids to correct and avoid volume depletion, correction of hypokalemia and
hypomagnesemia. Once daily dosing has been shown to be less toxic than multiple daily doses.
Gentamicin is usually dosed by ideal body weight. Various formulae exist for calculating
gentamicin dosage. Trough and peak serum levels of gentamicin are monitored during treatment
to individualize therapy and prevent excess exposure.
Gentamicin, like other aminoglycosides, causes nephrotoxicity by inhibiting protein
synthesis in renal cells. This mechanism specifically causes necrosis of cells in the proximal
tubule, resulting in acute tubular necrosis which can lead to acute renal failure. Psychiatric
symptoms related to gentamicin can occur. These include anorexia, confusion, depression,
disorientation and visual hallucinations. Immediate professional help should be sought if any of
these symptoms or others appear after administration of aminoglycosides. General medical
practitioners should refer patients with such symptoms to an otolaryngologist, commonly known
as an 'ear, nose, and throat doctor', for comprehensive tests.
A number of factors and determinants should be taken into account when using
gentamicin, including differentiation between empirical and directed therapy which will affect
dosage and treatment period. Many medical practitioners freely administer gentamicin as an
antibiotic without advising patients of the severe and permanent potential ramifications of its use.
Many people recover from gentamicin toxicity naturally over time if the drug is
discontinued, but they recover slowly and usually incompletely. Sometimes the toxicity of
gentamicin can still increase over months after the last dose. Upon cessation of gentamicin
therapy symptoms such as tinnitus and imbalance may become less pronounced. Sensori-neural
hearing loss caused by gentamicin toxicity is permanent however.

65. 65
 Mechanism of action
Gentamicin is a bactericidal antibiotic that works by irreversibly binding the 30S subunit
of the bacterial ribosome, interrupting protein synthesis. This mechanism of action is similar to
other aminoglycosides
 Gentamicin C complex and related components
Gentamicin is composed of a number of related gentamicin components and fractions
which have varying degrees of antimicrobial potency. The main components of gentamicin
include members of the gentamicin C complex: gentamicin C1, gentamicin C1a, and gentamicin
C2 which compose approximately 80% of gentamicin and have been found to have the highest
antibacterial activity. Gentamicin A, B, X, and a few others make up the remaining 20% of
gentamicin and have lower antibiotic activity than the gentamicin C complex. The exact
composition of a given sample or lot of gentamicin is not well defined, and the level of
gentamicin C components or other components in gentamicin may differ from lot-to-lot
depending on the gentamicin manufacturer or manufacturing process. Because of this lot-to-lot
variability, it can be difficult to study various properties of gentamicin including
pharmacokinetics and microorganism susceptibility if there is an unknown combination of
chemically related but different compounds.
 Production and usage in research
Gentamicin is produced by the fermentation of Micromonospora purpurea. It was
discovered in 1963 by Weinstein, Wagman et al. at Schering Corporation in Bloomfield, N.J.
working with source material (soil samples) provided by Rico Woyciesjes. Subsequently it was
purified and the structures of its three components determined by Cooper, et al., also at the
Schering Corporation. It was initially used as a topical treatment for burns at the Atlanta and San
Antonio burn units and was introduced into IV usage in 1971. It remains a mainstay for use in
sepsis.Gentamicin is also used in molecular biology research as an antibacterial agent in tissue
and cell culture, to prevent contamination of sterile cultures.

66. 66
4. Tetracycline
Tetracycline is a broad-spectrum polyketide antibiotic produced by
the Streptomyces genus of Actinobacteria,indicated for use against many bacterial infections.
It is a protein synthesis inhibitor. It is commonly used to treat acne today, and, more
recently, rosacea, and is historically important in reducing the number of deaths
from cholera. Tetracycline is marketed under the brand names Sumycin, Tetracyn,
Lymecycline, and Panmycin, among others. Actisite is a thread-like fiber formulation used in
dental applications. It is also used to produce several semisynthetic derivatives, which
together are known as the tetracycline antibiotics.
Tetracycline
Fig: Tetracycline structure
The term "tetracycline" is also used to denote the four-ring system of this compound;
"tetracyclines" are related substances that contain the same four-ring system.
It is on the World Health Organization's List of Essential Medicines, a list of the most important
medication needed in a basic health system.
 Medical uses
It is first-line therapy for rocky mountain spotted fever (Rickettsia), Lyme disease (B.
burgdorferi), Q fever (Coxiella), psittacosis and lymphogranuloma venereum(Chlamydia),
mycoplasma pneumoniae and to eradicate nasal carriage of meningococci. Tetracycline tablets
were used in the plague outbreak in India in 1992.

67. 67
 Spectrum of bacterial susceptibility
Tetracyclines have a broad spectrum of antibiotic action. Originally, they possessed some
level of bacteriostatic activity against almost all medically relevant aerobic and anaerobic
bacterial genera, both Gram-positive and Gram-negative, with a few exceptions, such
asPseudomonas aeruginosa and Proteus spp., which display intrinsic resistance. However,
acquired (as opposed to inherent) resistance has proliferated in many pathogenic organisms and
greatly eroded the formerly vast versatility of this group of antibiotics. Resistance
amongst Staphylococcus spp., Streptococcus spp., Neisseria gonorrhoeae, anaerobes, members
of the Enterobacteriaceae and several other previously sensitive organisms is now quite common.
Tetracyclines remain especially useful in the management of infections by certain obligately
intracellular bacterial pathogens such as Chlamydia, Mycoplasma and Rickettsia. They are also
of value in spirochaetal infections, such as syphilis, leptospirosis and Lyme disease. Certain rare
or exotic infections, including anthrax, plague and brucellosis, are also susceptible to
tetracyclines. These agents also have activity against certain eukaryotic parasites, including those
responsible for diseases such as malaria and balantidiasis.
The following represents MIC susceptibility data for a few medically significant
microorganisms:
Escherichia coli: 1 μg/ml - >128 μg/ml
Shigella spp.: 1 μg/ml - 128 μg/ml
 Mechanisms of resistance
Bacteria usually acquire resistance to tetracycline from horizontal transfer of a gene that
either encodes an efflux pump or a ribosomal protection protein. Efflux pumps actively eject
tetracycline from the cell, preventing the buildup of an inhibitory concentration of tetracycline in
the cytoplasm. Ribosomal protection proteins interact with the ribosome and dislodge
tetracycline from the ribosome, allowing for translation to continue.

68. 68
 Side effects
Use of the tetracycline antibiotics group is problematic; they can:
Stain developing teeth (even when taken by the mother during pregnancy)
Discolor permanent teeth (yellow-gray-brown), from infancy and childhood to eight years
old
Be inactivated by Ca2+
ion, so are not to be taken with milk, yogurt, and other dairy products
Be inactivated by aluminium, iron and zinc, not to be taken at the same time
as indigestion remedies (common antacids and over-the-counter heartburn medicines)
Cause skin photosensitivity, so exposure to the sun or intense light is not recommended
Cause drug-induced lupus, and hepatitis
Cause microvesicular fatty liver
Cause tinnitus
Interfere with methotrexate by displacing it from the various protein binding sites
Cause breathing complications, as well as anaphylactic shock, in some individuals
Affect bone growth of the fetus, so should be avoided during pregnancy
Fanconi syndrome may result by ingesting expired tetracyclines.
Caution should be exercised in long-term use with breastfeeding. Short-term use is safe;
bioavailability in milk is low to nil. According to the U.S. FDA, there are case reports
of Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme associated
with doxycyline use but a causative role has not been establihed.
Tetracycline hydrochloride is available as yellow crystalline powder Since tetracycline is
absorbed into bone, it is used as a marker of bone growth for biopsies in humans. Tetracycline
labeling is used to determine the amount of bone growth within a certain period of time, usually
a period of approximately 21 days.
Tetracycline is incorporated into mineralizing bone and can be detected by
its fluorescence. In "double tetracycline labeling", a second dose is given 11–14 days after the
first dose, and the amount of bone formed during that interval can be calculated by measuring the
distance between the two fluorescent labels. Tetracycline is also used as a biomarker
in wildlife to detect consumption of medicine- orvaccine-containing baits.