Antibiotics and

Bacterial Resistance

Prof. Dr. Mostafa A. Shalaby

Professor of Pharmacology
Faculty of Veterinary Medicine
Cairo University
Antibiotics
is a Double
Edged Weapon
 CONTENTS
● Definition of Antibiotics
● Action and Spectrum
● Chemical Groups
● Mode of Action
● Properties of an ideal antibiotic
● Basis of Antibiotic Combination
● Types & Mode of Action of Bacterial Resistance
● Selective Activity of Antibiotics
● Adverse or Toxic Effects of Antibiotics
■ Antibiotics are metabolites of living M.O.
during their growth and multiplication and
they can kill or stop the growth of other
pathogenic microorganisms
■ Methods of Antibiotic Manufacture

1- Biosynthetic Prepared by fluid extraction

of microorganisms in specific culture
culture media in Deep Vat (tank)
Fermentation method as • Penicillin G

2- Semisynthetic • Ampicillin
• Amoxicillin
• Methacycline
• Doxycycline
3- Synthetic • Chloramphenicol
 Bacterial Cell wall

Staphylococcus aurous

Pseudomonas aeruginosa
Microbial Sources of Antibiotics

1- Molds Penicillin G

2- Fungi All Antibiotics

3- B. Polymyxa Polymyxin B

4- B. Subtilis Bacitracin
Shapes of Some Bacteria
 Action of Antibiotics
Bacteriostatic Bactericide
■ Inhibit the growth ■ kill the bacteria in
of bacteria in vitro vitro
■ They need the ■ They do not need
immune body defense the immune body
mechanisms in vivo defense mechanisms
■ Examples ■ Examples
1- Tetracyclines 1- Penicillins
2- Macrolides 2- Cephalosporins
3- Lincosamides 3- Aminoglycosides
4- Chloramphenicol 4- Polypeptides
Antibacterial Action of Antibiotics
Activity of Some Antibiotics
Anaerobic G +Ve G ˗Ve
bacteria
Types of Killer Antibiotics

Concentration - Time - dependent

dependent killers killers

Aminoglycoside Penicillins
Fluoroquinolones Cephalosporins
Metronidazole Macrolides
Tetracyclines
By Increasing By Prolonging
concentration Exposure to
of antibiotic antibiotic
Sites of action of Antibacterial Drugs
 Spectrum of Antibiotics
Narrow Spectrum
■ Act against few types
of microorganisms i.e.
narrow range of
activity
Wide (Broad)
Spectrum
■ Act against wide range
of microorganisms as
Gm +ve, Gm – ve,
Rickettsia & Protozoa

■ Examples ■ Examples
Active mainly on Gm + ve 1- All Tetracyclines
● Penicillin G ● Oxacillin 2- Chloramphenicol
● Cloxacillin ● Tylosin 3- Ampicillin and Amoxicillin
● Rifamycin ● Novobiocin 4- Cephalosporins
Active mainly on Gm – ve 5- Gentamicin
● Streptomycin ● Colistin 6- Erythromycin
Chemical Groups
of Antibiotics
 Chemical Groups of Antibiotics

1- β Lactam Antibiotics

1- Penicillins 2- Cephalosporins

2- Aminoglycosides and Aminocyclitols

1- Streptomycin 2- Kanamycin 1- Spectinomycin

3- Neomycin 4- Gentamicin 2- Apramycin
5- Amikacin 6-Tobramycin
3- Tetracyclines
1- Oxytetracycline 2- Chlortetracycline
3- Tetracycline 4- Doxycycline
5- Minocycline 6- Methacycline
4- Macrolides and Lincosamides
1- Erythromycin 1- Lincomycin
2 Azithromycin 2- Clindamycin
3- Tylosin
4- Spiramycin
5- Polypeptides
1- Polymyxin B 2- Bacitracin Zinc
6- Miscellaneous
1- Chloramphenicol 2- Thiamphenicol 3- Florfenicol
 Antibiotics Combination
■ Goals
1- Reduce toxicity of the single antibiotic
2- Avoid incidence of bacterial resistance
3- Widen the spectrum of activity
• Doxycycline + Colistin • Tylosin + Neomycin
• Spiramycin + Neomycin • Erythromycin + Colistin
• Clindamycin + Spectinomycin
4- Increase efficacy by addition (1+1 =2)

• Spiramycin + Colistin • Sulpha + Trimethoprim

5- Increase efficacy by synergism (1+1 =3)
• Gentamicin + Carbenicillin
 Rules of Antibiotics Combination

I- Bactericide + Bactericide Synergistic (1+1=3)

• Gentamicin + Carbenicillin on Pseudomonas
• Amoxicillin + Colistin on E. Coli

II- Bacteriostatic + Bacteriostatic Synergistic

by addition (1+1=2)
• Clindamycin + Spectinomycin More active

III- Bactericide + Bacteriostatic Antagonistic

• Penicillin + Oxytetracycline Less active
 Basis of Selection of Antibiotics

1- Potency
8-Synergism
Or 2- Efficacy
Antagonism

9- Benefit
7- Bacterial
Risk 3- Action
Resistance
Cost

6-Toxicity 4- Spectrum
5- PK
profile
 Bacterial Resistance to Antibiotics
Definition
when bacteria are exposed to sub-inhibitory or sub-lethal
concentration of an antibiotic, emergence of resistant strains
occurs and the antibiotic becomes non effective

Acquired
Natural Transmissible
(Mutant)

Transformation Transduction Conjugation

Mechanisms of Resistance

1- Modified cell wall protein cause

inhibition of antibiotic uptake

2- Rapid efflux of antibiotic by

activation of efflux pumps
3- Inactivation of antibiotic by
enzymes

4- Alteration of a antibiotic
target sites
 3

4
2

1
2
(I) Natural Bacterial Resistance

1- E. coli are naturally resistant to

Penicillin G

2- Penicillin G can not penetrate the

cell wall of Gm – ve bacteria

3- Streptomycin can not penetrate the

cell wall of Gm + ve bacteria
(II) Acquired Bacterial Resistance
1- When M.O. change the permeability of
the cell membrane so tetracycline can
not accumulate in resistant bacteria

2- When M.O. develop genetic mutation so

bacterial resistance to streptomycin occr

3- When M.O. alter their metabolic pathway

necessary for their growth
(III) Transmissible Bacterial Resistance
The R- Plasmid is transferred by
1- Transformation: (in the Laboratory)
by transfer of free R-plasmid from
resistant to sensitive bacteria

2- Transduction
When bacteriophage carry R-plasmid
passes from one bacterium to the other
the R-plasmid convert sensitive
bacteria to resistant one
3- Conjugation (Sexual mating)
The R-Plasmid (Resistant factor) is divided within

resistant E. coli (Non pathogenic) and then pass

to sensitive Salmonella (pathogenic) by

conjugation via a temporary tube called pilus

Resistant Bacteria Sensitive Bacteria

Non pathogenic Pathogenic

 R Plasmid

Resistant B Sensitive B

Doner Pilus Recipient

Bacterial Resistance by Conjugation

Importance of Transmissible Resistance
1- Transmission of resistance between non
pathogenic E. coli to pathogenic
Salmonella

2- A single R- plasmid carry resistance to

several chemically unrelated
antibiotics
3- R-Plasmid can producetoxins so
resistant bacteria become more
dangerous
 Properties of Ideal Antibiotic
1- Potent, effective and specific for
the causative organism

2- Bactericide rather than Bacteriostatic

3- Broad spectrum rather than narrow

4- Rapidly attains to the site of infection

and maintain for sufficient period
Properties of Clinically Ideal Antibiotic

5- Cause no or minimal side effects or

toxicity to the host

6- cause No or short time residence in milk

in dairy animals

7- Cause no or low incidence of bacterial

resistance

8- Cause synergistic, but not antagonistic,

effects with other drugs
 Selective Toxicity of Antibiotics
Means that the antibiotic is toxic to
bacterial cells but Non toxic to
human or animal cells
This is expressed by
Therapeutic index (TI) (safety Margin)
The ratio of the lethal dose 50 to the
effective dose 50

LD50
TI = ---------------
ED50
 Selective toxicity of Antibiotics
Selective toxicity: Antibiotic are toxic
bacterial cells, but not to Human or animal
1- Human cells are complicated (Eukaryotic)
bacterial cells are simple (Prokaryotic)
2- Antibiotics accumulate in bacterial cells
at a higher Levels than in human cells
3-Bacterial cell contains 30 and 50S subunits
of ribosome but human cells contain
70 and 80S subunits of ribosome
4-Bacteria contain cell wall but human cells
contain no cell wall and contain plasma
membrane
Adverse Effect Examples

Nephrotoxicity Aminoglycosides
Ototoxicity
Neuromuscular
blockade
Irreversible Chloramphenicol
anemia
GIT disturbances Ampicillin
Diarrhea Tetracycline
Allergy and Rashes
Penicillin
Photosensitization Rifampicin
Toxicity of Aminoglycosides

Gentamicin Amikacin

Deafness
Prof. Dr. Mostafa Abbas Shalaby
Professor of Pharmacology
Faculty of Veterinary Medicine
Cairo University
Email: m_shalaby_1@outlook.com
Mobile: 0111 36 46 7 46