ANTIBIOTICS

Microbial Control
Antimicrobial Agents
 Concepts
- What is Antibiotics ?
- Classification of Antibiotics
- Use of Antibiotics
- Misuse of Antibiotics
- Antibiotic Resistance
The Discovery of Antibacterial Agents
1. In 1930s Gerhard Domagk discovered the anti-bacterial effect of
prontosil (=> sulfanilamide) => 1939 Nobel Laureate

2. Alexandre Fleming discovered that the mold Penicillium prevented

the multiplication of staphyloocci.
=> The first antibiotic, Penicillin, was identified => 1945 Nobel
Laureate
3. Streptomycin, tetracyclines & others were thereafter developed to
treat infectious diseases.
4. Bacteria start developing resistance to these agents
Antibiotics :

Substance (such as penicillin) that destroys or

inhibits the growth of other pathogenic
microorganisms and is used in the treatment of
external or internal infections.

While some antibiotics are produced by

microorganisms, most are now manufactured
synthetically
 Antibiotic /Antimicrobial
 Antibiotic: Chemical produced by a
microorganism that kills or inhibits the
growth of another microorganism.

 Antimicrobial agent: Chemical that kills or

inhibits the growth of microorganisms.
Microbial
Sources of
Antibiotics
Classification of antibiotics :
Antibiotics are classified several ways.
 On the basis of mechanism of action
 On the basis of spectrum of activity
 On the basis of mode of action
On the basis of mechanism of action:
Cell Wall Synthesis inhibitors:
Penicillins DNA Synthesis Inhibitors
Cephalosporins Fluoroquinolones(ciprofloxacillin)
Vancomycin Metronidazole
Beta-lactamase Inhibitors
Polymycin RNA synthesis Inhibitors
Bacitracin
Rifampin
Protein Synthesis Inhibitors
Mycolic Acid synthesis inhibitors
Inhibit 30s Subunit
Aminoglycosides (gentamycin) Isoniazid
Tetracyclines
Inhibit 50s Subunit Folic Acid synthesis inhibitors
Macrolides Sulfonamides
Chloramphenicol Trimethoprim
Clindamycin
On the basis of mechanism of action:
Inhibition of cell wall synthesis
(penicillins, cephalosporins, vancomycin, cycloserine, bacitracin)

 b-lactam drugs:
 Drugs containing a b-lactam
ring, e.g. penicillins and
cephalosporins.
 Vancomycin: bactericidal for
some gram-positive bacteria
 PBPs (penicillin-binding
proteins): receptors for b-
lactam drugs. There are 3-6
PBPs, some of which are
transpeptidation enzymes.
 Penicillins

 Produced by Penicillium chrysogenum

 Modifications:
 decrease acid lability;
 increase absorption;
 resistant to penicillinase;
 broader spectrum (e.g., ampicillin).
 b-lactamase inhibitors: bind b-lactamases irreversibly; combined use
with some penicillins to increase effectiveness.
 Modifications of cephalosporins were to expand their spectra or
increase their stability to b-lactamases.
 Vancomycin

A complex glycopeptide produced by Streptomyces

orientalis
Interacts with termini of the pentapeptide side chains

Inactive for gram-negative bacteria

Some enterococci have acquired resistance to

vancomycin
The resistance genes are carried on plasmids
 Polymyxins

 1. Cyclic polypeptides (from Bacillus polymyxa)

 2. Insert into bacteria outer membrane by

interacting with LPS and phospholipids 
increase cell permeability  bacterial cell
death
 3. Most Active for G-ve bacteria, because
G+ve bacteria have no outer membrane.
 Inhibition of protein synthesis

Aminoglycosides (streptomycin, kanamycin, neomycin,

gentamicin, tobramycin, amikacin, etc.): bind irreversibly to
30S ribosomal proteins and inhibit peptide formation;
bactericidal.
Tetracyclines: inhibit attachment of charged tRNA;
bacteriostatic.
Chloramphenicol: binds to peptidyl transferase of
ribosome; bacteriostatic.
Macrolides (erythromycins, clarithromycin, etc.): bind to
50S rRNA and block peptide elongation.
Inhibition of Nucleic Acid Synthesis (quinolones, rifampin, metronidazol, sulfonamides, trimethoprim)

.Quinolones and  Antimetabolites

fluoquinolones: blocking DNA
gyrase.
Sulfonamides: analogs of p-
Rifampin: inhibits RNA aminobenzoic acid (PABA) and
synthesis inhibit synthesis of folic acid,
which is an important precursor
to the synthesis of nucleic acids.
Metronidazol: effective to
anaerobic bacterial infections. Trimethoprim: inhibits
Reduction of its nitro group by dihydrofolic acid reductase in
bacterial nitroreductase synthesis of purines, methionine
produces cytotoxic compound and glycine.
that disrupts bacterial DNA.
On the basis of spectrum activity :
Broad spectrum antibiotics :
Amoxicillin
Tetracycline
 cephalosporin
Chlorampenicol
Erythromycin
Short spectrum antibiotics:
Penicillin –G
Cloxacillin
vancomycin
Bacitracin
Fluxacillin
On the basis of mode of action:
Bacteriostatic antibiotics
Tetracycline
Chlorampenicol
Erythromycin
Lincomycin
Bacteriocidal antibiotics
Cephalosporin
Penicillin
Erythromycin
Aminoglycosides
Cotrimoxazole
Antimicrobial activity in vivo
Factors affecting the
in vivo
effectiveness of antibiotics

 Environment  Concentration of antibiotic

 Amount of pathogen  Absorption
 State of bacterial metabolic  Distribution
activity (dormant state)  Variability of concentration
 Distribution of drug (unequally)
 Location of organism (intracell)
 Interfering substances
(complexity of biochemicals)
Ideal Chemotherapeutic
A useful chemotherapeutic agent should have in
vivo effectiveness and selective toxicity.
Other Attributes :
- Solubility
- Tissue stability
- Stable toxicity level
- Resistance Acquisition
- Allergenicity
Antibiotics
Pneumonia indications:
Syphilis 
 Sepsis  Respiratory Infections
 Meningitis  ENT Infections
 Osteomyelitis  Fungus Infections
 Urinogenital Infections
 Gall Infections
 Skin Infections
 Mucous Membrane
Infections
 Scarlet Fever
 Diphtheria
Antibiotics Susceptibility Test
Following diagnosis (when causative agent of clinical infection
is known), the drug of choice is often be selected on basis of
current experience, otherwise laboratory tests for antibiotic
susceptibility are necessary to determine the drug of choice.
Antibiotic Sensitivity test (disc diffusion susceptibility test)
- commonly performed when the microbe recovered is of a type
that often resistant to antimicrobial drugs (e.g. G-ve enteric
bacteria).
- Measuring sizes of zones of growth inhibition (single or multi
discs) and compared with sizes of standard provided.
Antibiotic sensitivity test
Bacitracin Test
The Misuse of Antibiotics
Antibiotic misuse, sometimes called antibiotic abuse or
antibiotic overuse (i.e. indiscriminate use).
 The misuse or overuse of antibiotics, may produce serious
effects on health.
 It is a contributing factor to the creation of multidrug-resistant
bacteria, informally called "super bugs" relatively harmless
bacteria can develop resistance to multiple antibiotics and
cause life-threatening infections.
 Antibiotic Resistance
A seminar topic
- Define resistance (laboratory & clinically)
- Origin of drug resistance.
- Cross resistance.
- Limitation of drug resistance.
- Clinical implications of drug resistance.
- Sensitivity test