Inhibiting the growth of

pathogens in vivo using

antimicrobial agent
 THE ANGELITE
PRAYER
Almighty God, we glorify you for giving us the Angelite
Charism. We thank you for the gift of your Son, Jesus Christ,
who is the Way, Truth, and Life. We bless you for the
continuous guidance of the Holy Spirit.

Grant us, we pray, courage and strength that we may give

perpetual praise to you in whatever we do. We ask this
through Christ, our Lord. Amen.

Oh, Holy Guardian Angels, guide us and protect us!

Laus Deo semper!
CORE VALUES

EXCELLENCE
Definition of Terms

Chemotherapeutic
Antimicrobial Antibiotic
Drugs

Antifungal Antiparasitic Antiviral

Chemotherapeutic
Agents
• Chemotherapy is the use of any
chemical (drug) to treat any disease or
condition.

• A chemotherapeutic agent is any drug

used to treat any condition or disease.

• Chemotherapeutic agents are

collectively referred to as anti microbial
agents
Anti Microbial
Agents
• An antimicrobial agent is any chemical
(drug) to treat an infectious disease,
either by inhibiting or killing pathogens
in vivo.

• Some antimicrobial agents are

antibiotics.

• An antibiotic is a substance produced

by a microorganism that kills or inhibits
growth of other microorganisms.
Historical Note

Alexander Fleming (1928)

• First Antibiotics
• Growth of Penicillium notatum A
mould colonies inhibiting
growth of staphylococcus
bacteria.
• Penicillin – inhibitory B
substance produced by mould.
C
Characteristics of an Ideal Antimicrobial
Agent
The 5 most common mechanisms of action of antimicrobial agents
are:
• Inhibition of cell wall synthesis
• Damage to cell membranes
• Inhibition of nucleic acid synthesis (either DNA or RNA synthesis)
• Inhibition of protein synthesis
• Inhibition of enzyme activity

• What characteristics should an ideal antimicrobial agent

have?
Antibacterial Agents
• Drugs used to treat bacterial diseases
are called antibacterial agents; those
used to treat
• Fungal diseases, antifungal agents;
• Protozoal diseases, antiprotozoal
agents;
• Viral diseases, antiviral agents
• Bacteriostatic drugs inhibit growth of
bacteria (sulfa drugs)
• Bacteridal drugs kill bacteria
(penicillin)
• Narrow Spectrum antibiotic (Colistin
and nalidixic acid destroy only Gram-
negative bacteria )
• Broad spectrum Antibiotic (Antibiotics
that are destructive to both Gram-
positive and Gram-negative bacteria
such as ampicillin, chloramphenicol
and tetracycline)
• Multidrug therapy
Some Major Categories of Antibacterial Agents

Penicillins Cephalosporins Carbapenems

Glycopeptides Tetracyclines Aminoglycosides

Macrolides Flouroquinolones Multidrug therapy

Some Major Categories of Antibacterial
Agents
Penicillin
• Bactericidal drug
• β lactam drugs –molecular
structure -4-sided ring structures
• interfere with cell wall synthesis
• maximum effect on bacteria that
are actively dividing.
• Penicillin G/ Penicillin V referred
to as natural penicillins
• natural penicillins -effective
against some gram positive
(streptococcus)and anaerobic
bacteria. Some gram negative (N.
meningitis)
Cephalosporins
• Bactericidal
• β lactam antibiotic, are also
produced by moulds
• interfere with cell wall synthesis.
• Classified into:
• 1st gen (gram positive bacteria)
• 2nd gen (gram negative bacteria)
• 3rd gen (greater activity against
gram negative bacteria)
• 4th gen (gram positive and
negative)
• 5th gen (expanded activity against
aerobic gram-positive cocci)
Some Major Categories of Antibacterial
Agents

Tetracyclines
• Bacteriostatic
• inhibit protein synthesis
• Effective against a wide variety
of bacteria
• Chlamydia, V. cholerae etc.
Aminoglycosides
• Bactericidal
• inhibit protein synthesis.
• Major factor that limits their
use is their toxicity.
• Effective against wide variety
of aerobic gram-negative
bacteria.
• Ineffective against anaerobes
• E. coli, Klebsiella,
Some Major Categories of Antibacterial
Agents
Macrolides
• Bacteriostatic at lower doses
• Bactericidal at higher doses
• inhibit protein synthesis
• Chlamydia, T. pallidum, H.
influenzae
• Erythromycin, clarithromycin,
azithromycin
Fluoroquinolones
• Bactericidal
• inhibit DNA synthesis
• Most common: Ciprofloxacin
• Levofloxacin / Moxifloxacin –
broad spectrum agents with
activity against both gram
positive and gram-negative
bacteria
Some Major Categories
of Antibacterial Agents
Multi Drug Therapy
• single antimicrobial agent is not sufficient to
destroy all pathogens that develop during the
course of the disease

• 2 or more drugs are used simultaneously to kill

all the pathogens and to prevent resistant
mutant pathogens from emerging.

• Mycobacteruin tuberculosis

• Isoniazid, rifampin, pyrazinamide, ethambutol

Antibacterial Agents - Synergism Versus
Antagonism
Synergism
• 2 antimicrobial agents are
used together to produce a
degree of pathogen killing that
is greater that that achieved by
either drug alone.
• Synergism is a good thing!
- 2+2=6
Antagonism
• 2 drugs work against each
other.
• The extent of pathogen killing
is less than that achieved by
either drug alone.
Antagonism is a bad thing!
- 2+2=1
Anti fungal
Agents
• Most antifungal agents work in one of 3
ways:
- By binding with cell membrane sterols
(e.g., nystatin and amphotericin B)
- By interfering with sterol synthesis
(e.g., clotrimazole and miconazole)
- By blocking mitosis or nucleic acid
synthesis (e.g., griseofulvin and 5-
flucytosine)
Antiparasitic
Agents
• Are usually quite toxic to the
host and works by;
• Interfering with DNA and
RNA synthesis
• Interfering with metabolism
(metronidazole)
Antiviral Agents

• Antiviral agents are the newest weapons in

antimicrobial methodology.

• Difficult to develop these agents because

viruses are produced within host cells.

• Some drugs have been developed that are

effective in certain viral infections, but not
others; they work by inhibiting viral
replications within cells.

• Antiviral agent “cocktails” (several drugs

that are administered simultaneously) are
being used to treat HIV infection.
Drug Resistance:
“Superbugs”
• Superbugs are microbes (mainly bacteria) that
have become resistant to one or more
antimicrobial agent.
• Infections caused by superbugs are difficult to
treat!
• Bacterial superbugs include:

- methicillin-resistant Staphylococcus aureus

(MRSA)

- vancomycin-resistant Enterococcus spp. (VRE)

- multidrug-resistant Mycobacterium
tuberculosis (MDRTB)
Mechanisms by which Bacteria Become
Resistant to Antimicrobial Agents

MECHANISM EFFECT
1. A chromosomal mutation that causes 1. The drug cannot bind to the bacterial
change in the structure of a drug cell
binding site
2. A chromosomal mutation that causes
a change in cell membrane 2. The drug cannot pass through the cell
permeability membrane and thus cannot enter the
cell
3. Acquisition (by conjugation,
transduction or transformation) of a 3. The drug is destroyed or inactivated
gene that enable the bacterium to by the enzyme
produce an enzyme that destroys or
inactivated the drug
4. Acquisition (by conjugation,
transduction or transformation) of a 4. The drug is pumped out of the cell
gene that enables the bacterium to before it can damage or kill the cell
produce a multidrug-resistance
(MDR) pump
Drug Resistance
and ß-Lactamases

• Every penicillin and cephalosporin

molecule contains a B-lactam ring.

• Some bacteria produce the

enzyme B-lactamases that destroy
this ring
• Drug companies have developed
special drugs that combine a B-
lactam antibiotic with a B-
lactamase inhibitor.
 What strategies do you
think should be included
in in the War Against
Drug Resistance?
What other factors should be considered by clinicians before starting
antibiotic therapy?
Why should antimicrobials not be used indiscriminately?
Thank you