PRINCIPLES

OF
ANTIMICROBIA
L THERAPY
 LEARNING
OBJECTIVES
• Describe the various mechanism by which
antibiotics/antimicrobial drugs work
• Discuss the rational use/applications of
antimicrobial drugs at field level.
• Enhance skills of the technical and clinical
use of antimicrobial drugs in the future.
 Course content
• Mechanism/mode of action
• Spectrum of activity
• Bactericidal and bacteriostatic
• Combination of antibiotic therapy
INTRODUCTION
Define antimicrobials/Antibiotic and antibacterial
drugs?
• Antimicrobial drugs:
Is any substance of natural, synthetic or semi-synthetic origin
that kills or inhibits the growth of a microorganism but
causes little or no host damage.
• Antibiotic:
Is a substance produced by a microorganism that, at low
concentration, inhibit or kills other microorganisms
Remark:
Antimicrobial and antibiotic are often times used
interchangeably
Antibacterial:
Drugs that inhibit or destroy the growth of bacteria
Successful antimicrobial
therapy is based on 4
principles:-
1. Identification and characteristic of the
pathogen(s), includes its antimicrobial
sensitivity and selection of a drug
based on the sites of infection
2. Effective concentration of the indicated
antimicrobial agent for sufficient period
at the site of infection.
3. A dose rate, frequency and route of
administration of the antimicrobial agent,
as well as duration of therapy, that
maximizes the likelihood of a cure,
prevents relapse and minimizes the risk
of resistance without causing any harmful
drug – induced effects in the animal.
4. Specific and appropriate supportive
therapy to enhance the animals ability to
overcome the infection and associated
disease condition
 Classes of antibiotics
 Classification of antibacterial drugs that are
major use in vet. medicine
Are of six major classes of antibiotics:
1. Aminoglycosides (Streptomycin, neomycin,
Kanamycin, gentamicin) .
2.Cephalosporins (cephacetril, cephaloride,
cefachlor etc.
3.Macrolides (erythromycin, Tylosin, spiramycin,
timicosin)
4. Penicillins (Benzylpenicillns, Cloxacillin,
aminobenzyl-penicillins )
5.Quinolones (nalidixic acid, ciprofloxacin,
etc)
6. Tetracyclines (oxytetracycline, Tetracyclines
L.A and Doxycline etc.
 What are the mechanisms
of action of
antimicrobial/antibiotics?
The mechanisms of action of antibacterial fall into
four categories or groups:
a) Inhibition of cell wall synthesis,

b)Alteration of cell membrane permeability,

c) Inhibition of nucleic acid synthesis or function,

and

d) Inhibition of protein synthesis.

I) Inhibition of cell wall synthesis

An intact bacterial cell wall keeps the

bacterium from filling with water and
bursting, thus the drug acts by
inhibiting of an enzyme in the synthesis
of the cell wall

Several agents affect cell-wall synthesis,

the most important being Penicillins,
Cephalosporins, Bacitricin and
Vancomycin
 II) Alteration in cell
membrane permeability
They act on the phospholipid layer of the cell
membrane to alter permeability
The drugs have specificity for a particular microbial
group based on difference in types of lipids in
their cell membranes.
For instance polymyxins interact with phospholipids
and cause leakage, particularly in gram negative
bacteria

Ex. Polymyxin B
 III) Inhibition of protein
synthesis
• Aminoglycosides , Tetracyclines, Chloramphenicol, Macrolides and
Lincomycin all act by interfering with the normal development of
the protein combinations necessary for bacterial growth.
• In the growth phase, the process of linking together amino acids to
form a new bacterial cell has to proceed in a cyclical fashion and
any interruption of the cycle locks the process at the point of
interference and growth is halted.
• Because of the continuation of process which may have been
affected by the interrupting mechanism, the overall integration of
cell metabolism is disrupted and the long-term effect is so severe
that the cell dies.
 IV) Inhibition of nucleic
acid synthesis
• May block synthesis of nucleotides, inhibit
replication or stop transcription
• Sulfonamides and trimethoprim block enzymes
required for DNA and RNA synthesis
• In some cases drug also competes with normal
substrate for enzymes active site
 Spectrum of action of
antibiotics
• Antibiotic spectrum of action refers to the range
of bacteria on which a specific class of antibiotic
is effective.
1.Narrow spectrum – Drugs acting only on a single
or limited group of microorganisms. i.e. isonazid
is only active against mycobacteria, penicillins
are primarily effective against gram (+)
bacteria.
2.Broad spectrum – drugs acting on a wide variety
of microorganisms. Ex. Tetracyclines,
chloramphenical, etc
Spectrum cont.
Activity (range) of various antimicrobial classes.
Bacteria Mycoplasma Rickettsia Chlamydia Protozoa

Aminoglycosides + +

Beta-lactams +

Chloramphenicol + + + +

Lincosamides + + +

Macrolides + + +
Pleuromutilins + + +

Tetracyclines + + + +

Quinolones + + + +

Sulfonamides + + + +

Trimethoprim + +
 Bactericidal and
Bacteriostatic
• Bactericidal antibiotics KILL the bacteria and the total
number of viable organisms decreases.
• Batericidal activity may occur if concentration of these
antibiotics are high enough.
• In addition the RATE and EXTENT of animicrobial activity
may be:-
- Concentration dependent (aminoglycosides)
- concentration and time dependent (floroquinolones)
- Time dependent (beta-lactams)

• Example of bacreicidal drugs, Chloramphenicol,

Cephalosporins, Polymoxin, Vancomycin, Beta – lactams,
Aminoglycosides, etc.
• Bacteriostatic antibiotics ARREST the
GROWTH and REPLICATION of bacteria at
serum levels achievable in the patient,
thus limiting the spread of infection while
the body’s immune system attacks,
immobilizes and eliminates the pathogen
Ex. Tetracyclines, Lincomycin, Macrolides
• All antimicrobials are bacteriostatic at some
concentration
• Some antimicrobials are bacteriostatic at almost all
concentrations
• Some antimicrobials are capable of bactericidal
activity if concentrations are high enough
(and maintained for long enough in some
cases)
• Some antibacterial agents inhibit the growth of the
bacterium at one concentration, the minimum
inhibitory concentration (MIC) (es, 0.25 ug/ml), but
a higher concentration, the minimum bactericidal
concentration (MBC), is necessary to kill it (eg, 4.0
ug/ml).
 Antimicrobial drug
combination
Knowledge of the different mechanisms of action of
antimicrobials provides some ability to predict their
interaction when they are used in combination.
• Indifferent or additive
This is when the combined effects of the drugs equal
the sum of their independent activities measured
separately.
• Synergistic
Action of the combination are significantly greater than
the independent effects.
For instance facilitation of drug entry of one antibiotic
by another, i.e. beta-lactam and aminoglycoside
 Antagonist
Action of the combination is significantly less than
the sum of the actions of each component
• Most commonly cited is "bacteriostatic drug
inhibits action of bacteriocidal".
• Antagonism may occur if antibacterial
combinations involve
1. Inhibition of bactericidal activity such as treatment
of meningitis in which a bacteriostatic drug
prevents the bactericidal activity of another
2. Competition for drug-binding sites such as
macrolide- Chloramphenicol combinations (of
uncertain clinical significance)
 Antibiotic Resistance
Mechanisms
1.Altered permeability of the bacteria to an
antibacterial agent – altered permeability
may be due to the inability of the bacterial
agent to enter the bacterial cell.
2.Inactivation of the antimicrobial agent
3.Altered target site
4.Replacement of a sensitive pathway
THE
END