A Review on antibiotics and bacterial resistance

1. ANTIBIOTICS
Presented by:
E. Madhan Mohan
Associate Professor
Department of Pharmacology,
SCHOOL OF PHARMACY,
Nalla Narasimha Reddy Education Society’s Group of Institutions.
1NNRG SCHOOL OF PHARMACY6 MAY 2016

2. Contents
 Introduction to Pharmacology
 Difference between animal cell & Bacterial cell
 Types of bacteria
 Antibiotics- Classification.
 Mechanism of action of various antibiotics.
 Bacterial resistance
 Conclusion
 References
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3. Introduction to Pharmacology
Pharmacology: (derived from 2 Greek words: Pharmakon-drugs
and logos-science).
 Pharmacology is the branch of science deals with the
study of various drugs on living system.
 It includes physicochemical properties, biochemical and
physiological effects, mechanism of action, therapeutic
uses and adverse effects of drugs.
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4. Difference between Animal cell and Bacterial cell
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Eukaryotic cell: e.g. Animal Prokaryotic cell: e.g. Bacteria

5. Types of Bacteria
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6. Types of Bacteria
 Peptidoglycan is the material that makes up bacterial cell walls
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Thicker Peptidoglycan layer
but not outer membrane
means gram +ve
Thinner Peptidoglycan layer
with an outer membrane
means gram -ve

7. Types of Bacteria
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Gram-Positive Bacteria Gram-Negative Bacteria
Simple cell wall. More complex cell wall.
Thick peptidoglycan cell wall layer. Thin peptidoglycan cell wall layer.
No outer lipopolysaccharide wall
layer.
Contain outer lipopolysaccharide
wall layer.
Retain crystal violet/iodine. Retain safranin.
Appear blue/purple.
Appear pink/red.
Eg. Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus viridans group
Bacillus anthracis
Corynebacterium diphtheriae
Eg. Neisseria gonorrhoeae
Neisseria meningitidis
Escherichia coli
Haemophilus inuenzae
Salmonella typhi

8. Mode of Transmission of Bacterial Infections
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9. ANTIBIOTICS
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Definition:
These are substances produced by microorganisms or
synthetically which selectively suppress the growth of or kill
other microorganisms at very low concentrations.

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Classification of
Antibiotics:
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MECHANISM OFACTIONS
Inhibition of cell
wall synthesis
Inhibition of
bacterial protein
synthesis
Inhibition of
Nucleic Acid
Synthesis
Inhibition of
Folic Acid
Synthesis
Penicillins
Cephalosphorins
Imipenem
Meropenem
Aztreonam
vancomycin
Aminoglycosides
Chloramphenicol
Macrolides
Tetracycline
Streptogrmins
linezolid
Fluoroquinolones
Rifampin
Sulfonamides
Trimethoprim
Pyrimethamine

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Inhibition of Cell wall synthesis:
Beta-Lactam Antibiotics:
These are antibiotics having a β-lactam ring. The
two major groups are penicillins and cephalosporins.
1. PENICILLINS:
Eg: Penicillin-G, Penicillin V, Amoxicillin,
Ampicillin, Cloxacillin.
2. CEPHALOSPORINS:
Eg: Cefixime, Cefpodoxime proxetil, Cephalexin,
Cefuroxime axetil
Bacteria cell wall unique in construction
•Contains peptidoglycan layer.
Antimicrobials that interfere with the synthesis of cell
wall do not interfere with eukaryotic cell.
• Due to the lack of cell wall in animal cells.

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Mechanisms of Action:
Penicillins and cephalosporins are considered bactericidal.
The weakness in the cell wall causes the cell to lyze.
Competitively inhibits function of Penicillin-binding proteins
Inhibits peptide bridge formation between glycan molecules
This causes the cell wall to develop weak points at the growth
sites and become fragile.
Penicillins are more effective against Gram+ve bacteria. This
is because Gram + bacteria have penicillin binding proteins
(PBPs) on their walls.
The cephalosporins have low affinity to penicillin-binding
proteins of Gram + bacteria, therefore, are enter into the bacteria
through porin channels most effective against Gram –ve
bacteria.

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Mechanism of resistance:
By enzyme Penicillinases: break the beta
lactam ring structure.
Structural changes in PBP’s.
Change in porin structure: concerns the
gram negative organism
Uses: Pharyngitis, rheumatic fever, pneumonia,
Gonorrhoea, Syphilis, Diphtheria etc.
ADR’S: Local irritancy, Toxicity to the brain,
convulsions and coma, Hypersensitivity, fatal
anaphylaxis, nephrotoxicity, heamotological
disorders, Diarrhea etc.

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• Inhibition of protein synthesis:
– Structure of prokaryotic ribosome acts as target for many
antimicrobials of this class
• Differences in prokaryotic and eukaryotic ribosomes responsible for
selective toxicity
– Drugs of this class include
1. Aminoglycosides 3. Chloramphenicol
2. Tetracyclins 4. Macrolids (Erythromycin)

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1. Aminoglycosides
E.g: Gentamicin, streptomycin and
tobramycin
MOA:
Irreversibly binds to 30S ribosomal
subunit
Causes distortion and malfunction of
ribosome
Blocks initiation translation
Causes misreading of mRNA
Uses: Tuberculosis, Plague,
Meningitis
ADR’S: with extended use
include
Otto toxicity,
Nephrotoxicity,
Neuromuscular blockade.

16. 2. Tetracyclins:
Reversibly bind 30S ribosomal subunit
• Blocks attachment of tRNA to ribosome
– Prevents continuation of protein
synthesis
– Effective against certain Gram + and Gram -
– Newer tetracyclines such as doxycycline
have longer half-life
• Allows for less frequent dosing
Uses: Cholera, Plague,
Rickettsial infections etc.
ADR’S: Can cause discoloration
of teeth if taken as young
child, Liver damage, Kidney
damage, Phototoxicity
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3. Chloramphenicol:
Binds to 50S ribosomal subunit
Prevents peptide bonds from forming
and blocking proteins synthesis
Effective against a wide variety of
organisms
Uses:
Generally used as drug of last resort for
life-threatening infections, typhoid fever,
meningitis, conjunctivitis
ADR’S:
Rare but lethal side effect is Bone
marrow depression, Hypersensitivity
reactions, Gray baby syndrome

18. 4. Macrolides antibiotics:
Eg: Erythromycin, clarithromycin and azithromycin
– Reversibly binds to 50S ribosome
• Prevents continuation of protein synthesis
– Effective against variety of Gram +
organisms and those responsible for
atypical pneumonia
– Often drug of choice for patients allergic to
penicillin
Uses: respiratory infections, rheumatic fever,
Diphtheria, Syphilis and gonorrhea etc.
ADR’S: Mild-to-severe epigastric pain,
reversible hearing impairment,
Hypersensitivity, Jaundice.
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Mechanisms of resistance:
A mutation of ribosomal binding site
Enzymatic modification of antibiotic
An active efflux of antibiotic out of cell

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Inhibition of Nucleic Acid Synthesis:
Eg: Fluoroquinolones
(levofloxacin, norfloxacin, Ciprofloxacin),
Rifampin
Bacteriocidal
Can inhibit DNA gyrase or RNA polymerase
Uses: urinary antiseptic, Gonorrhoea
Gastroenteritis, Typhoid:
ADR’S: g.i. upset and rashes.
neurological—headache, drowsiness,
vertigo, visual disturbances, occasionally
seizures
Mechanism of resistance:
an alteration of alpha subunit of DNA gyrase
(chromosomal)
beta subunit of RNA polymerase
(chromosomal) is altered

21. Inhibition of Folic Acid Synthesis:
Eg: Sulfonamides, Trimethoprim,
Pyrimethamine, Cotrimaxazole.
 Bacteriostatic
 Binds and blocks enzymes mainly folate
synthase, dihydrofolate reductase
responsible for folic acid synthesis.
• What are Folic Acid?
Folic acid is necessary for the synthesis of amino acids,
hence necessary for bacterial protein synthesis.
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22. Uses: Trachoma, conjunctivitis,
for preventing infection on burn
surfaces,
malaria etc.
ADR’S: Nausea, vomiting.
Crystalluria,
Hypersensitivity reactions,
Hepatitis,
Haemolysis
Mechanism of resistance:
Mutations in the gene for
dihydrofolate reductase
decreasing binding affinity .
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23. Interference with cell membrane integrity:
Few damage cell membrane
• Polymixn B most common
– Common ingredient in first-aid
skin ointments
Binds membrane of Gram -ve
cells
• Alters permeability
– Leads to leakage of cell and
cell death
• Also bind eukaryotic cells but to
lesser extent
– Limits use to topical
application
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24. RESISTANCE- A MOJAR PROBLEM WITH THE
USAGE OF ANTIBIOTICS
• Mechanisms of resistance
– Drug inactivating enzymes
• Some organisms produce
enzymes that chemically modify
drug
– Penicillinase breaks β-lactam
ring of penicillin antibiotics
– Alteration of target molecule
• Minor structural changes in
antibiotic target can prevent
binding
– Changes in ribosomal RNA
prevent macrolides from binding
to ribosomal subunits
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25. RESISTANCE- A MOJAR PROBLEM WITH THE
USAGE OF ANTIBIOTICS
• Mechanisms of resistance
– Decreased uptake of the drug
• Alterations in porin proteins decrease
permeability of cells
– Prevents certain drugs from entering
– Increased elimination of the drug
• Some organisms produce efflux
pumps
– Increases overall capacity of
organism to eliminate drug
» Enables organism to resist
higher concentrations of drug
» Tetracycline resistance
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26. Antibiotics Vs Severe Adverse drug reactions
• Otto toxicity,
• Nephrotoxicity,
• Teratogenic effects,
• Bone marrow depression,
• Loss of blood cells,
• Hypersensitivity reactions,
• Hepatitis etc.
Are Challenging the usage of antibiotics.
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27. Conclusion:
• Though antibiotics are able to
control the growth of
microorganisms, the WHO advised
to restrict the usage of antibiotics
unless usage is needful.
• Use antibiotics with proper
DIAGNOSIS.
• Use antibiotics when the causative
organism is known
• It is advisable to use low dose of
multiple antibiotics instead of high
dose of single antibiotic.
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28. References
• Rang and Dale, Pharmacology, 6th edition, 2007, pg.685– 690.
• Bertram G. Katzung, Basic & Clinical pharmacology, 11th
edition, 2009, pg.1070 – 1076.
• Goodman & Gilman's The Pharmacological Basis of
Therapeutics. 10th edition, pg. 1565-1578.
• Lippincott's Illustrated Reviews Pharmacology, 4th Edition,
pg.529 – 535.
• K.D.Tripati, Essentials of Medical pharmacology, 6th
edition,2008, pg.727 – 738.
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