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 disease-

causing 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, SulfonamidesAntifungal synthetic drugs - Amphotericin, ketoconazoleAntiviral agents - Acyclovir, AmantadineAntiparasitics (nematodes, protozoa, amoebae) - Metronidazole, ChloroquineAntihelminthics - 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 pre-

exposed 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 AntibioticsBroad 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 theintestines, lungs and bladder.

The destruction of the body's normal bacterial flora provides an opportunity for drug-resistant microorganisms to grow vigorously and can lead to a secondary infection such asCandidiasis in females.

Example - Amoxicillin, Amoxicillin/Clavulanic acid, Carbapenems, Levofloxacin, Gatifloxacin,Moxifloxacin, Ciprofloxacin, Streptomycin,Tetracycline, Chloramphenicol, Cephalosporin etc.

Narrow Spectrum AntibioticsNarrow 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 bacterialcell 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 (differentbinding 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 cell’s 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 allliving forms, including bacteria. Some antibiotics work by binding to components involved inthe process of DNA or RNA synthesis, which causes interference of the normal cellularprocesses 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 cellularprocesses essential for the survival of the bacterial pathogens. Antibiotics disrupt the folicacid pathway, which is a necessary step for bacteria to produce precursors important forDNA synthesis.

Inhibits folic acid synthesis by competing with p-amino benzoic acid (PABA) and bind todihydropteroate 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 vitaminsynthesized by bacteria, but not humans.

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

5. Chemical Structure Class

Natural AntibioticsNon-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 post-

treatment 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 cross-

linking 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 PenicillinThe 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 toother Penicillins such as penicillin V and ampicillin. The levels of drug in blood are high andstable with administration of Amoxicillin.

• Synthesis- Amoxicillin is a semi synthetic aminopenicillin antibiotic structurally related to thepenicillin 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 onlyexceptions 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 antibioticscompared 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.

CephalosporinThe core of Cephalosporin antibiotics have an additional six membered, heterocyclic, sulphur-containing two

ring system which includes a β-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 penicillin’s 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 beta-

lactamase 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 beta-

lactamase 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 Gram-

negative 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 α-

amino group at position C-7. This structure makes them vulnerable to hydrolysis by β-

lactamases.

The basic structure of first generation cephalosporin

2nd generation Cephalosporin'sSecond 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 α- iminomethoxy group to the C-7 side chain. This gave an increased

resistance to β- 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 tRNA’s.

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 - Trimethoprim and Sulfamethoxazole in a 1:5 ratio. Drug type - DNA synthesis inhibitor Primary target - Tetrahydrofolic acid synthesis inhibitors Pathways affected - 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 DrugsDifferent 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 sulfonamide-

resistant 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.