Lecture 6 Antibiotics and Resistance

11/5/2022
BMS271
General Microbiology for Dental Students
ANTIMICROBIAL AGENTS
Dr. Waleed Eldars

Professor of Medical Microbiology
and Immunology
Faculty of Medicine
Mansoura University
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Anti-Microbial Agents
Definition: include antibiotics, anti-viral and
anti-fungal drugs.
Mechanism of action of clinically used
antibiotics:
• Inhibition of cell wall synthesis.
• Alteration of cell- membrane permeability.
• Inhibition of protein synthesis.
• Inhibition of nucleic acid synthesis.
• Other mechanisms of action.
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A)Cell Wall Inhibitors
Cell wall
inhibitors
β- Lactams Glycopeptides Polypeptides
Penicillins Cephalosporins Monobactams Carbapenems
Aztreonam Imipenem
Cell Wall Inhibitors
I.  Lactam antibiotics
1. Penicillin
2. Monobactam
3. Carbapenem
4. Cephalosporins
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Mechanisms of action:
• Penicillins and cephalosporins act through the
inhibition of the terminal cross- linking of the
peptidoglycan.
Resistance to penicillin:
• The organism produce penicillin destroying
enzyme ß- lactamases
• Absence of penicillin receptors.
I.  Lactam antibiotics - Penicillins

Natural penicillins (Penicillin • Gram positive organisms, Neisseria and some
G): anaerobes.
Extended-spectrum penicillins
• Active against many strains of Gram negative
(Aminopenicillins; e.g. bacteria.
Amoxycillin):
Carboxypenicillins (e.g. • More active than aminopenicillins against most

Carpenicillin): Enterobacteriaceae and Pseudomonas aeruginosa.
• Greater activity than carboxypenicillins against

Ureidopenicillins (Pipracillin): Pseudomonas aeruginosa.
Penicillinase-resistant
• Active against penicillinase-producing Staphylococci.
penicillins (e.g. Methicillin):
Co-Drugs (Beta-lactam + β- • Additional activity against β-lactamase producing

lactamase inhibitor): organisms, e.g. Clavulanic acid plus Amoxycillin.
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I.  Lactam antibiotics - Monobactam
• Aztreonam (Azactam):
- Resistant Gram-negative bacteria.
- Pseudomonas.
I.  Lactam antibiotics - Carbapenem
• Imipenem (Tinam)
- Resistant Gram-negative & Gram-positive
bacteria.
- Pseudomonas.
I.  Lactam antibiotics - Cephalosporin
1st G 2nd G 3rd G 4th G 5th G

G+ve> G-ve G+ve = G-ve G-ve > G+ve G+ve = G-ve G+ve = G-ve
MRSA
Pseudomonas X Pseudomonas √
Cephalexin Cefuroxime Cefotaxime Cefepime Ceftaroline
Cephdroxil Cefaclor Ceftriaxone
Cefdinir
11/5/2022 3:51:08 PM Dr. Medhat A. Eldaker
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II. Glycopeptides
• Vancomycin
- Resistant Gram-positive bacteria.
- MRSA.
III. Polypeptides
A. Cycloserine
- TB
B. Bacitracin
- Diagnostic 11
- Topical
Protein Synthesis Inhibitors
30 S 50 S
Aminoglycoside Tetracycline Macrolide Chloramphenicol
Bactericidal Bacteriostatic Bactericidal Both
G –ve & Pseudo- vibrio G +ve> -ve Enteric fever
monas
Gentamicin Oxytetracyclin Erythromycin Chloramphenicol
Amikacin Doxycyclin Azithromycin
Tobramycin Clindamycin
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DNA Replication Inhibitors

I. Sulphonamides
• Bactiristatic
Inhibition of
• UTI-Chemoprophylaxis precursor
- e.g Trimethoprim.
II. Quinolones
• Bactricidal Inhibition of DNA

• Broad spectrum gyrase
- Ofloxacin - Ciprofloxacin
-Levofloxacin
III. Rifampicin
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• Bactricidal Inhibition of RNA
• TB polymerase
Cytoplasmic membrane Inhibitors
Polyenes
• Bacteiristatic
- Polymyxin B  topical
- Mitronidazole  anaerobes
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Antibiotic Combinaton
Administration of more than one antibiotic is called antibiotic
combination.
Additive (indifferent)
Synergistic effect: Antagonistic effect:
effect:
• The activity of two • The activity of two • The activity of two
drugs in combination drugs in combination drugs in combination
is equal to the sum is greater to the sum is less to the sum (or
(or a partial sum) of of their independent a partial sum) of
their independent activity when studied their independent
activity when studied separately, may activity when studied
separately. occurs by: separately.
• Sequential block of
a metabolic
pathway.
• One drug may
facilitate the entry
of the second drug.
• One drug may
inhibit the enzymes
produced by
bacteria.
ANTIBIOTIC COMBINATION
• Indications for the clinical use of antimicrobial

combinations:
• Prevention of the emergence of resistant
organisms.
• Polymicrobial infection.
• Initial therapy (the source of infection is not
clear yet).
• Decreased toxicity.
• Synergism
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Causes of failure of antimicrobial

chemotherapy:
• Clinical condition not suitable to antibiotic treatment (as
viral infection or mixed bacterial infection).
• Failure to use laboratory properly.
• Wrong choice of antibiotics.
• Inadequate doses of the antibiotics.
• Inadequate duration of treatment by the antibiotics.
• Wrong route of administration.
• Use of antagonistic antibiotic combination.
• Development of antimicrobial resistance.
Drug resistance
• It is the unresponsiveness of the organisms to the given
drug (antibiotics).
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Origin of drug resistance:

The origin of drug resistance may be:
Genetic origin:
• Chromosomal resistance: this results after
spontaneous mutation in a locus that controls
susceptibility to antimicrobial drug (change
receptors, permeability).
• Extra chromosomal resistance (plasmids):
• Plasmids genes for antimicrobial resistance often
control the formation of enzymes capable of
destroying the drug.
Mechanisms of Drug resistance:

Microorganisms produce enzymes that destroy the drug: as β- lactamases
enzymes produced by Staphylococci to destroy the β-lactams.
Microorganisms decrease their permeability to the drug.
Microorganisms develop an altered structural target for the drug: As

alteration of the receptor protein that give attachment to the drug.
Microorganisms develop an altered metabolic pathway that bypasses the

reactions inhibited by the drug.
Microorganisms develop an altered enzyme that can still perform its

metabolic function but is much less affected by the drug.
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A B C
RESISTANT BACTERIAL STRAINS:
• Methicillin resistant Staphylococcus aureus

(MRSA).
• Vancomycin resistant Staphylococcus aureus
(VRSA).
• Vancomycin resistant enterococci (VRE).
• Quinolone Resistant Clostridium difficile.
• ESBL- Gram negative Bacilli.
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Summary and Rap UP
Thank you
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11/5/2022

Dr. Waleed Eldars

A)Cell Wall Inhibitors

β- Lactams Glycopeptides Polypeptides

Penicillins Cephalosporins Monobactams Carbapenems

Cell Wall Inhibitors

Cell Wall Inhibitors

I.  Lactam antibiotics - Penicillins

Carboxypenicillins (e.g. • More active than aminopenicillins against most

• Greater activity than carboxypenicillins against

Co-Drugs (Beta-lactam + β- • Additional activity against β-lactamase producing

Cell Wall Inhibitors

I.  Lactam antibiotics - Monobactam

I.  Lactam antibiotics - Carbapenem

I.  Lactam antibiotics - Cephalosporin

1st G 2nd G 3rd G 4th G 5th G

11/5/2022 3:51:08 PM Dr. Medhat A. Eldaker

Cell Wall Inhibitors

Protein Synthesis Inhibitors

DNA Replication Inhibitors

• Bactricidal Inhibition of DNA

Cytoplasmic membrane Inhibitors

• Indications for the clinical use of antimicrobial

Causes of failure of antimicrobial

Origin of drug resistance:

Mechanisms of Drug resistance:

Microorganisms decrease their permeability to the drug.

Microorganisms develop an altered structural target for the drug: As

Microorganisms develop an altered metabolic pathway that bypasses the

Microorganisms develop an altered enzyme that can still perform its

RESISTANT BACTERIAL STRAINS:

• Methicillin resistant Staphylococcus aureus

Summary and Rap UP

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