Antimicrobials - The word was derived from the Greek words anti (against), mikros (little)

and bios (life) and refers to all agents that act against microbial organisms.
This is not synonymous with antibiotics. Antimicrobial agent is a chemical substance
derived from a biological source or produced by chemical synthesis that kills or inhibits the
growth of microorganisms.
Humans, and our domestic animals, can serve as hosts to a wide variety of diseasecausing organisms (pathogens): Bacteria,Viruses, Fungi, Protozoan, Helminthes (worms).
Antimicrobial drugs are two categories Antibiotics - Antimicrobial drugs produced by microorganisms.
Synthetic (Chemotherapeutic ) drugs.
Antimicrobial Drugs by Susceptible Organisms Antibacterial synthetic drugs - Penicillin G, Erythromycin, Cephalosporins, Sulfonamides
Antifungal synthetic drugs - Amphotericin, ketoconazole
Antiviral agents - Acyclovir, Amantadine
Antiparasitics (nematodes, protozoa, amoebae) - Metronidazole, Chloroquine
Antihelminthics - Albendazole, Mebendazole, Praziquantel

Criteria for Ideal Antimicrobials

Selective toxicity
No hypersensitivity
Penetrate tissues quickly
Resistance not develop quickly
No effect on normal flora
Broad spectrum

Antibiotics
Antibiotics - An antibiotic (Greek: anti, "against", and bios, "life") is a natural substance or
compound that is produced by one microorganism e.g. bacteria, fungi, actinomycetes or
synthetically and has the ability to harm other or kills or inhibits their growth. Antibiotic
is from antibiosis, meaning against life.

The noun antibiotic was first used in 1942 by Dr. Selman A. Waksman, soil microbiologist.
Dr. Waksman and his colleagues discovered several actinomycetes derived antibiotics. 1928
Fleming discovered penicillin, produced by Penicillium.

Antibiotics are medications that can help to treat some infections and save lives.

Antibiotics work on various types of infections caused by bacteria. They do not work with
infections that are caused by a virus, such as colds, flus and most sore throats.

They include family medications such as, amino glycosides, macrolides, Penicillin, tetracyclines,
and cephalosporin etc.

The first Sulfonamide and first commercially available antibacterial Prontosil was developed.

Root of administration
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: Erythromycin, Clindamycin, Gentamycin,Tetracycline
Treatment Bacterial infection
Protozoan infection, e.g., Metronidazole is effective against several Parasitic.
Immunomodulation, e.g., Tetracycline, which is effective in periodontal inflammation and
Dapsone, which is effective in autoimmune diseases.
Treatment with antibiotics has proven to work, with almost no cases of remission.
Prevention of infection Surgical wound
Dental antibiotic prophylaxis
Conditions of neutropenia, e.g. cancer-related

Classification of Antibiotics
Antibacterial antibiotics are commonly classified based on their -

1.Chemical/Biosynthetic Origin
2.Biological Activity
3.Spectrum of Activity
4.Mechanism of Action
5.Chemical Structure

Antibacterial Agents
1. Chemical/Biosynthetic Origin
Natural - Mainly fungal sources; More toxic than synthetic antibiotics. Ex- Benzyl
Penicillin Gentamicin,Aminoglycosides.

Semi-synthetic - Chemically-altered natural compound; Decrease toxicity and

increase

effectiveness. Ex-

Ampicillin, Beta-lactam

antibiotics, Cephalosporins,

Carbapenems.

Synthetic - chemically designed in the lab; Designed to have even greater

effectiveness and less toxicity. Ex- Moxifloxacin, Norfloxacin, sulfonamides, Quinolones,
Oxazolidinones.

Organisms develop resistance faster to the natural antimicrobials because they have been preexposed to these compounds in nature.
There is an inverse relationship between toxicity and effectiveness as you move from natural
to synthetic antibiotics.

2. Biological Activity :

Bactericidal drugs : Kill the microorganisms are called

bactericidal drugs .
Ex - Penicillin, Cephalosporin, Monobactams, Carbapenems,
Fluoroquinolones (Ciprofloxacin), Glycopeptides (Vancomycin)

Bacteriostatic drugs : Arrest the growth or replication

of the microorganism but cannot kill them.
Ex - Tetracyclines, Spectinomycin, Sulphonamides, Macrolides,
Chloramphenicol,Trimethoprim

It should be noted that a drug may be bacteriostatic for one

organism but bactericidal for another.

3. Spectrum of Activity :
The ability a drug kills or suppresses the growth of microorganisms.
Broad Spectrum
Narrow Spectrum

Broad-spectrum Antibiotics
Broad Spectrum Antibiotics - The drugs that have a wide antimicrobial scope (gram
positive , gram negative bacteria and rickettsias).
Advantages
Broad-spectrum antibiotics are properly used in the following medical situations.
when there is a wide range of possible illnesses and a potentially serious illness would result
if treatment is delayed.
Used against drug resistant bacteria that do not respond to others.
Use in the case of superinfections, where there are multiple types of bacteria causing illness,
thus warranting either a broad-spectrum antibiotic or combination antibiotic therapy.
Show prophylaxis action after an operation.
Disadvantages
Antibiotics can change the body's normal microbial content by attacking indiscriminately
both the pathological and naturally occurring, beneficial or harmless bacteria found in the
intestines, lungs and bladder.
The destruction of the body's normal bacterial flora provides an opportunity for drugresistant microorganisms to grow vigorously and can lead to a secondary infection such as
Candidiasis in females.
Example - Amoxicillin, Amoxicillin/Clavulanic acid, Carbapenems, Levofloxacin, Gatifloxacin,
Moxifloxacin, Ciprofloxacin, Streptomycin,Tetracycline, Chloramphenicol, Cephalosporin etc.

Narrow Spectrum Antibiotics

Narrow Spectrum Antibiotics - The drugs that only act on one kind or one strain of
bacteria(selected organism).
Advantages:

The narrow-spectrum antibiotic will not kill as many of the normal microorganisms in the
body as the broad spectrum antibiotics. So, It has less ability to cause super infection.

The narrow spectrum antibiotic will cause less resistance of the bacteria as it will deal with
only specific bacteria.

Disadvantages:

Narrow spectrum antibiotics can be used only if the causative organism is identified.

If you don't choose the drug very carefully, the drug may not actually kill the microorganism
causing the infection.

Example - Azithromycin, Clarithromycin, Clindamycin, Erythromycin,Vancomycin etc.

4. Modes of Action or Mechanism of Action

A. Protein synthesis inhibitors
B. Cell wall synthesis inhibitors
C. Nucleic acid or RNA / DNA inhibitors
D. Metabolic enzyme / viral enzyme inhibitors
E. Plasma membrane-injuring agents
F. Essential cell constituents synthesis inhibitors

Mechanism of Action of Antibiotics

Inhibitors of cell wall synthesis - While the cells of humans and animals do not have cell walls,
this structure is critical for the life and survival of bacterial species.
Inhibit transpeptidation (enzymes involved in cross-linking the polysaccharide chains of the bacterial
cell wall peptidoglycan).Then Activate cell wall lytic enzymes. Ex - Penicillin , Cephalosporin
Prevent transpeptidation of peptidoglycan subunits by binding to D-Ala-D-Ala amino acids (different
binding site ) at the end of peptide side chains. Ex - Vancomycin

Inhibitors of cell membrane function - Cell membranes are important barriers that segregate
and regulate the intra and extracellular flow of substances. A disruption or damage to this structure
could result in leakage of important solutes essential for the cells survival.

Bind to plasma membrane and disrupts its structure and permeability properties. Ex - Polymyxin B
Inhibits folic acid synthesis by competing with p-amino benzoic acid (PABA). Ex - Sulfonamides
Blocks folic acid synthesis by inhibiting the enzyme tetrahydrofolate reductase. Ex - Trimethoprim
Exact mechanism is unclear, but it is thought to inhibit lipid synthesis (especially mycolic acid); putative
enoyl-reductase inhibitor. Ex - Isoniazid

Mechanism of Action of Antibiotics

Inhibitors of protein synthesis - Enzymes and cellular structures are primarily made of
proteins. Protein synthesis is an essential process necessary for the multiplication and
survival of all bacterial cells. Several types of antibacterial agents target bacterial protein
synthesis by binding to either the 30S or 50S subunits of the intracellular ribosome. This
activity then results in the disruption of the normal cellular metabolism of the bacteria, and
consequently leads to the death of the organism or the inhibition of its growth and
multiplication.

Bind to small ribosomal subunit (30S) and interfere with protein synthesis by directly
inhibiting synthesis and causing misreading of mRNA. Ex- Amino glycosides ,Tetracycline
Bind to 23S rRNA of large ribosomal subunit (50S) to inhibit peptide chain elongation during
protein synthesis. Ex- Macrolides, Chloramphenicol

Antibiotics: Modes of Action

Mechanism of Action of Antibiotics

Inhibitors of nucleic acid synthesis - DNA and RNA are keys to the replication of all
living forms, including bacteria. Some antibiotics work by binding to components involved in
the process of DNA or RNA synthesis, which causes interference of the normal cellular
processes which will ultimately compromise bacterial multiplication and survival.
Inhibit DNA gyrase and topoisomerase-II, thereby blocking DNA replication.
Ex - Quinolones and Fluoroquinolones
Inhibits bacterial DNA-dependent RNA polymerase. Ex Rifampin
Inhibitors of other metabolic processes - Other antibiotics act on selected cellular
processes essential for the survival of the bacterial pathogens. Antibiotics disrupt the folic
acid pathway, which is a necessary step for bacteria to produce precursors important for
DNA synthesis.
Inhibits folic acid synthesis by competing with p-amino benzoic acid (PABA) and bind to
dihydropteroate synthase. Ex - Sulfonamides
Blocks folic acid synthesis by inhibiting the enzyme tetrahydrofolate reductase. Ex
Trimethoprim
Both of these enzymes are essential for the production of folic acid, a vitamin
synthesized by bacteria, but not humans.

5. Chemical Structure Class

Amino Acid Derivatives

D- Cycloserine

Aminoglycosides

Gentamicin, Kanamycin, Neomycin, Spectinomycin,Tobramycin

Aureolic Acids

Chromomycin

Aziridines

Mitomycin

Benzenoids

Herbimycin

Benzimidazoles

Albendazole, Ricobendazole

Beta - lactam

Amoxicillin, Dicloxacillin, Ampicillin, Penicillin G, Benzathine Penicillin,

PenicillinV, Cefaclor, Cefixime, Cefotaxime, Ceftriaxone, Cephradine

Coumarin-glycosides

Coumermycin, Novobiocin sodium

Fatty Acid Derivatives

Cerulenin

Glucosamines

1-Deoxymannojirimycin hydrochloride

Glycopeptides

Bleomycin sulfate, Vancomycin hydrochloride

Imidazoles

Clotrimazole, Econazole nitrate, Ketoconazole, Metronidazole

Indol Derivatives

Staurosporine

5. Chemical Structure Class

Macrolactams

Ascomycin

Macrolides

Azithromycin, Clarithromycin, Clindamycin Erythromycin,

Rifampicin,Tylosin,Virginiamycin

Nucleosides

Ribavirin,Tunicamycin

Peptides

Actinomycin D, Bacitracin, Cyclosporin A, Polymyxin B

Peptidyl Nucleosides

Puromycin dihydrochloride

Phenicoles

Chloramphenicol,Thiamphenicol

Polyenes

Nystatin, Amphotericin B

Pyridines and Pyrimidines

Isoniazid,Trimethoprim, Tioconazole

Quinolones and Fluoroquinolones

Ciprofloxacin, Lomefloxacin, Nalidixic acid, Ofloxacin

Statins

Mevastatin

Steroids

Fusidic acid

Sulfonamides

Sulfadiazine, Sulfasalazine, Sulfacetamide

Tetracycline

Tetracycline, Chlortetracycline, Oxytetracycline,

Doxycycline, Doxorubicin, Duramycin

Natural Antibiotics
Non-pharmaceutical - A wide range of chemical and natural compounds are used as
antimicrobials. Organic acids are used widely as antimicrobials in food products, e.g.
lactic acid, citric acid, acetic acid, and their salts, either as ingredients, or as disinfectants.
For example Beef carcasses often are sprayed with acids, and then rinsed or steamed, to reduce
the prevalence of E. coli.
Many essential oils included in herbal pharmacopoeias are claimed to possess
antimicrobial activity, including: Cinnamon oil, Clove oil, Eucalyptus oil, Garlic,
Oregano oil, Lemon oil, Mint oil, Neem oil, Peppermint oil, Sandalwood oil etc.
Onion - Onion contains phytoncides substances with bactericidal and anti-fungal
effect. In particular, phytoncides kill the Diphtheria and tubercle bacillus of Koch. Just
one piece of onion can kill all the hazardous microbes in the mouth cavity. Fresh onions
are used to cure colds, flu, rhinitis and sore throat. Fresh onion mush applied to the
burns, can reduce the pain and irritation of the skin, preventing blisters and infection.

Natural Antibiotics
Camomile - Camomile tea contains oleic acid, palmitic acid, linoleic acid, salicylic acid and
stearic acid; carotene, vitamin C and essential oils. Camomile has antibacterial, anti-microbial,
anti-viral, antispasmodic, anti-inflammatory and wound healing effect.

Honey - Healing effect of honey is known since ancient times. It contains about 300
ingredients: vitamins, amino acids, proteins, enzymes, micro- and macro-elements. It has
antiseptic, antibacterial and anti-fungal properties, thus killing germs. Honey is used as natural
antibiotic for the treatment of inflammation in the upper and lower airways, gastrointestinal
tract and small pelvis. Moreover honey prevents infection of open wounds, healing cuts.
Regular intake of honey increases metabolism and strengthens immunity.

Echinacea - Echinacea is prescribed for the treatment of flu, hepatitis and herpes. It is
effective almost in every disease of: urinary tract, infections and colds, administered as posttreatment of antibiotics.

Beta - lactams

This particular group is characterized by its four-membered, nitrogen-containing beta-lactam

ring at the core of their structure, which is key to the mode of action of this group of
antibiotics.The Beta lactams are effective only against actively growing bacteria.

Beta lactam antibiotics target the penicillin-binding proteins or PBPs (peptidoglycan) - a

group of enzymes found anchored in the cell membrane, which are involved in the crosslinking of the bacterial cell wall.

The beta-lactam ring portion of this group of antibiotics binds to these different PBPs,
rendering them unable to perform their role in cell wall synthesis.

This then leads to death of the bacterial cell due to osmotic instability or autolysis.

Penicillin
The penicillins are derived from certain species of Penicillium (e.g. P. notatum and P.
chrysogenum). The penicillin are the oldest class of antibiotics, and have a common chemical
structure which they share with the cephalosporin. The natural penicillins are based on the
original penicillin G structure.
The various natural penicillins have been designated as F, G, K, O, and X. Penicillin G is the most
satisfactory type to manufacture and use and 90% of commercially available penicillin is of
this type. The beta - lactam structure is iconic for all antibiotics of the penicillin family and is
important in sequestering the penicillin binding protein (PBP) involved in bacterial cell wall
synthesis.
Mechanism of action : the drugs weaken the cell wall ,causing the bacterium to take up
excessive amounts of water and then rupture.
Penicillinases (Beta - lactamases) : Enzymes that cleave the beta - lactam ring and thereby
render penicillin and other beta - lactam antibiotics inactive.

Penicillins

Difference between Amoxicillin and Penicillin

The discovery of antibiotics has led to increased use of the compounds as drugs. Amoxicillin and
Penicillin are two such antibiotics. Penicillin is the first generation antibiotic having similar
functions but differing in efficacy.

Absorption- Amoxicillin is better absorbed from the gastrointestinal tract compared to

other Penicillins such as penicillin V and ampicillin. The levels of drug in blood are high and
stable with administration of Amoxicillin.

Synthesis- Amoxicillin is a semi synthetic aminopenicillin antibiotic structurally related to the

penicillin family. Penicillin is synthetic penetrates less and hence less effective.

Efficacy- Amoxicillin is more effective and acts against a wide range of pathogenic microbes.

Penetration into tissues- Amoxicillin penetrates better into tissues than penicillin. The only
exceptions are brain tissues and spinal fluid.

Safety- Both are suitable for use in pregnancy and in paediatrics.

Cost- Both antibiotics are cheaper and are available in generic formulations.

Duration of treatment- Treatment with Amoxicillin requires fewer courses of antibiotics

compared to Penicillin.These can be taken for a short while.

Action- Both of them act on the bacteria by inhibiting cell wall formation.

Source- Both drugs are produced from the mold penicillium.

Cephalosporin
The core of Cephalosporin antibiotics have an additional six membered, heterocyclic, sulphur-containing two
ring system which includes a -lactam ring condensed with dihydrothiazine ring. The core itself can also
be referred to as 7-aminocephalosporanic acid. Modification of side chains on the relevant positions has
been used to create a whole new class of cephalosporin antibiotics. Modification of side-chains in
position 7 of the lactam ring seems to affect the antibacterial activity while position 3 of the
dihydrothiazine ring alters pharmacokinetic properties and receptor binding affinity.
These are natural products that have been chemically modified in the laboratory. Produced from Penicillium
by converting one of the methyl group of thiazolidine ring into six member dihydrothiazine. They are
similar to penicillins in their mechanism of action i.e. disrupts the synthesis of the peptidoglycan layer of
bacterial cell walls. Cephalosporin are usually preferred agents for surgical prophylaxis. They are widely
used to treat gonorrhea, meningitis, and staphylococcal and streptococcal infections.

Consequently, The "Cepha" drugs are among the most diverse classes of antibiotics,
and are themselves sub grouped into 1st,

2nd, 3rd and 4th generations. Each

generation has a broader spectrum of activity. The generation system is based on

different antimicrobial activity shown by different cephalosporins.
There are few chemical and activity features that could be used for classification, for
example chemical structure, side chain properties, pharmacokinetic, spectrum of
activity or clinical properties.

 1st Generation Cephalosporin (C1G): Narrow spectrum; good Gram-positive activity

and relatively modest Gram-negative activity. Inactivated by Gram-negative beta- lactamases.
Ex - Cefazolin, Cephalexin
2nd generation cephalosporin (C2G): Better Gram-negative coverage (more betalactamase stability). Ex - Cefacor, Cefuroxime
3rd generation cephalosporin (C3G): Wider spectrum of action when compared to
C1G and C2G. Less active than narrow spectrum agents against Gram-positive (better betalactamase stability). Ex - Ceftriaxone, Cefotaxime
4th generation cephalosporin (C4G): Broadest spectrum of action. Active against high
level cephalosporinases. Ex - Cefpirome, Cefepime
Next generation cephalosporin: Broad spectrum; active against the common Gramnegative bacteria. Some Gram-positive activity. Has Bactericidal activity. Not yet FDA
approved. Ex - Ceftobiprole, Ceftaroline

First generation cephalosporins have good antimicrobial activity against gram-positive

bacteria but limited activity against gram-negative species. The chemical structures of the first
generation cephalosporins are fairly simple. All have a single methyl group at position C-3.
The methyl group at position C-3 gives low affinity for common PBP which can explain the
relatively low activity of these first drugs. All of the first generation cephalosporins have an amino group at position C-7. This structure makes them vulnerable to hydrolysis by lactamases.

The basic structure of first generation cephalosporin

2nd generation Cephalosporin's

Second generation cephalosporins are very similar in basic structure to the first generation.
Loracarbef however does not have the normal dihydrothiazin ring but is a carbacephem that has
a carbon atom in the ring instead of a sulfur atom making it a tetrahydropyridine ring. This
chemical property gives Loracarbef better stability in plasma while retaining oral absorption
characteristics and affinity for binding to PBP. The 7-phenyl-glycine makes it orally available
and the chlorine at position C-3 makes it as active as Cefaclor.
An important structural change in the development of second generation cephalosporins was
the introduction of an - iminomethoxy group to the C-7 side chain. This gave an increased
resistance to - lactamases due to stereochemical blocking of the beta-lactam ring.

Fluroquinolones
Unlike the penicillin and cephalosporin classes, flouroquinolones are not based on natural
products but are completely synthetic (initial starting compound is nalidixic acid).
Flouroquinolones function to inhibit proper unwinding of bacterial DNA during replication
thereby halting the process and resulting in cell death.
The fluroquinolones are broad-spectrum bactericidal drugs.
Exam First generation

Nalidixic acid

Second generation

Ciprofloxacin, Norfloxacin, Ofloxacin, Levofloxacin

Third generation

Gatifloxacin

Fourth generation

Moxifloxacin, Gemifloxacin

Tetracycline
Tetracyclines are four membered ring structures with various functional groups attached
produced by bacteria of the Streptomyces species.
They disrupt protein synthesis by binding to the larger portion of the cellular ribosome, thus
blocking the attachment of amino acid bound tRNAs.
Broad-spectrum bacteriostatic agents, the tetracyclines may be effective against a wide variety of
microorganisms, including rickettsia and amebic parasites.

Amino glycosides
Amino glycosides inhibit protein synthesis in a generally similar mechanism as tetracyclides and
macrolides.

Macrolides
Produced by Streptomyces erythraeus, have a complex structure characterized by
a large lactone ring with two sugar molecules attached via glycoside bonds.
Antibiotics in this class inhibit protein synthesis in a functionally similar way as
tetracyclines.
Erythromycin, the prototype of this class, has a spectrum and use similar to
penicillin. Newer members of the group, azithromycin and clarithyromycin, are
particularly useful for their high level of lung penetration. Clarithromycin has
been widely used to treat Helicobacter pylori infections, the cause of stomach
ulcers.

Effects of Combinations of Drugs

Antagonism occurs when the effect of two drugs together is less than the effect of either
alone.
Ibuprofen (anti-diuretic properties) + diuretic
Penicillin + streptomycin

Synergism occurs when the effect of two drugs together is greater than the effect of either
alone.
Sulfamethoxazole and Trimethoprim
Penicillin with beta - lactamase inhibitor (clavulonic acid)
Alcohol and sleeping pills

Co - trimoxazole

Combination
Drug type
Primary target
Pathways affected

- Trimethoprim and Sulfamethoxazole in a 1:5 ratio.

- DNA synthesis inhibitor
- Tetrahydrofolic acid synthesis inhibitors
- Nucleotide biosynthesis and DNA replication

Trimethoprim + Sulfamethoxazole: Synergism

Nucleoside and Nucleotide Analogs

Drug resistance
Drug resistance is the phenomenon that susceptibility of pathogenic microorganisms to
drugs becomes lower or even loses after the microorganisms contact with drugs many times.

What is antimicrobial resistance I?

The ability of a microorganism to survive at a given concentration of an antimicrobial agent
at which the normal population of the microorganism would be killed.
This is called the Epidemiological breakpoint.

What is antimicrobial resistance II?

The ability of a microorganism to survive treatment with a clinical concentration of an
antimicrobial agent in the body.
This is called the Clinical breakpoint.

When the bacteria show resistance to one drug, they are also resistant to some other
drugs.This phenomenon is called cross drug resistance.
Types of resistance
1.

Intrinsic or natural resistance - e.g. no target site in the bacteria.

2.

Acquired resistance

Microbes may elaborate drug-metabolizing enzymes (i.e. penicillinase).

Microbes may cease active uptake of certain drugs.

Microbial drug receptors may undergo change resulting in decreased antibiotic binding
and action.

Microbes may synthesize compounds that antagonize drug actions.

Resistance acquired by mutation is unusual.

Resistance acquired by R-factors on plasmids is common. (R factor contains genes

coding for enzymes that make the cell resistant to antibiotics)

How do bacteria become resistant to antibiotics?

Bacteria develop resistance for several reasons:
a)

Antibiotics are give appropriately for months or years for life threatening conditions.

b)

Antibiotics are given appropriately for acute infections but are taken inappropriately
(missing doses or failing to take all the antibiotics ordered by the provider).

c)

Antibiotics are either ordered by a provider or purchased in a foreign country for

infections that do not require antibiotics, such as colds, sore throats, flu and some cases of
food poisoning.

d)

This is why it is so important to use antibiotics for only bacterial infections. In the past,
antibiotics may have been prescribed inappropriately, even sometimes for viral infections.
Antibiotics should not be used for these viral infections because they don't help in treating
symptoms, and they may cause side effects.

e)

Overuse of antibiotics contributes to the emergence of more resistant bacteria, which may
not respond to commonly used, inexpensive antibiotics.

Resistance to Antimicrobials Drugs

Different mechanisms by which microorganisms exhibit resistance to drugs.
A. Microorganisms produce enzymes that destroy the active drug.
Ex- Staphylococci resistant to Penicillin G produce a beta - lactamase that destroys the drug.
Other beta-lactamases are produced by gram-negative rods.
B. Microorganisms change their permeability to the drug.
Ex- Tetracycline accumulate in susceptible bacteria but not in resistant bacteria. Resistance to
polymyxins is also associated with a change in permeability to the drugs.
C. Microorganisms develop an altered structural target for the drug.
Ex- Chromosomal resistance to aminoglycosides is associated with the loss or alteration of a
specific protein on the 30S subunit of the bacterial ribosome that serves as a binding site in
susceptible organisms.

D. Microorganisms develop an altered metabolic pathway that bypasses the reaction

inhibited by the drug.
Ex- Some sulfonamide-resistant bacteria do not require extracellular PABA but, like
mammalian cells, can utilize preformed folic acid.
E. Microorganisms develop an altered enzyme that can still perform its metabolic
function but is much less affected by the drug than the enzyme in the susceptible
organism.
Example: in some sulfonamide-susceptible bacteria, the tetrahydropteroic acid
synthetase has a much higher affinity for sulfonamide than for PABA. In sulfonamideresistant mutants, the opposite is the case.

What should consider when using antibiotics?

Antibiotics are considered to be a "miracle cure," and they continue to provide significant benefits when
used wisely. In order to maintain our ability to treat serious bacterial infections effectively, it is important
that you remember the following items:

Carefully follow health care provider's advice and recommendations. Antibiotics should only be used
when prescribed by health care provider. Provider will determine what form of treatment is best suited
for illness and related symptoms. If prescribing an antibiotic is deemed appropriate, provider will then
select the one that will work best for treating specific infection. Provider will also provide with a
sufficient amount of medication and will instruct on proper dosage.

Always complete the medication. Antibiotics must be taken for the full amount of time prescribed by
health care provider. Do not stop taking the antibiotics when symptoms go away. Stopping the treatment
may allow some of the bacteria to continue to live and become resistant to the antibiotic prescribed.

Antibiotics should not be saved and reused. As mentioned before, should always take the full course of
antibiotic treatment, so none of the drug should be "left over."

Do not take them in merely feel sick.

Different types of infections require different types of antibiotics, so taking leftover medications is often
not effective.

Why not use Two Antibiotics all the time?

Antagonism
Cost
Increased risk of side effects
May actually enhance development of resistance inducible resistance
Interactions between drugs of different classes
Often unnecessary for maximal efficacy

Side effects to using Antibiotics

Antibiotics can cause unfavorable reactions such as nausea, diarrhea, and stomach pain etc.

Some people experience an allergic reaction that can be characterized by a rash and itching,
or difficulty breathing in severe cases. Some of these allergic reactions can be fatal.

Some antibiotics kill naturally occurring bacteria that are needed by the body. In these
instances bacteria that can cause diarrhea or yeast infections replace the "good" bacteria.

Harmful Reactions of Antibiotics

A. Hypersensitivity or Allergy - Penicillin is particularly notorious in this respect. Skin

rashes, joint pains, and anaphyltic-like manifestations may result following penicillin therapy.

B. Induction of Bacterial Resistance - The organisms develop resistance to a given

antibiotic.

C. Effect on the Replacement Flora - Prolonged use of the antibiotics tends to

encourage multiplication of undesirable organisms like Proteus or Pseudomonas species
which maybe harmful to the host.

D. Toxic Interactions - Several of the antibiotics will interact with other drugs and with
each other to produce ototoxicosis. kanamycin, neomycin, streptomycin, vancomycin, and
other ototoxic drugs such as furosemide and ethacrynic acid may have progressive
cumulative effects that can be addictive and may produce permanent deafness. Tetracycline,
administered parenterally, may interact with methoxyflurane to produce an impairment of
renal functions which may have fatal outcome.

Harmful Reactions of Antibiotics

E. Interactions at the Receptor Site - Many of the antibiotic drugs exert

pharmacodynamic effects in the host in addition to their effects on the infecting
pathogen.
Several antibiotics produce neuromuscular blockade by competitive antagonism of
acteylcholine at the myoneural junction. Bacitracin, streptomycin, gentamicin, kanamycin,
neomycin, paromomycin, polymyxin B have additive neuromuscular blocking effects
among themselves and with other neuromuscular blocking agents.
Tetracyclines may enhance the rate of development of cachexia because they exert an
antianabolic effect.They would increase the catabolic effect of flucocorticoids.
Chloramphenicol may interfere with antibody production in active immunization
proceudres, eg., immune response to tetanus toxoid.

Chemotherapeutic agent (drug)-any chemical

(semisynthetic or synthetic) that is used in
medicine. Ideally, it should attack microorganisms
selectively and not harm human cells.