ANTIMICROBIAL

THERAPY

Eka Sukmawaty, S.Si., M.SI

UIN ALAUDDIN MAKASSAR 2015

The History of Antimicrobial
Agents

It Start in 1928, when Alexander Flemming

found contamination on his bacterial
culture!

He decided to isolate the antimicrobial

substance!
 GENERAL PROPERTIES OF
ANTIMICROBIAL AGENTS
Selective Toxicity
For internal use, an antimicrobial drug
must have selective toxicitythat is, it
must harm the microbes without
causing significant damage to the host.
toxic dosage level VS therapeutic
dosage level
chemotherapeutic index is defined as the
maximum tolerable dose per kilogram of body weight,
divided by the minimum dose per kilogram of body
weight, that will cure the disease.
 The Spectrum of Activity
The range of different microbes against which an
antimicrobial agent acts is called its spectrum of
activity.
Broad Narrow

if the identity of the organism

A broad-spectrum drug is
especially useful when a patient
is seriously ill with an infection
caused by an unidentified
organism
is known, a narrows pectrum
drug should be used
such a drug minimizes the
destruction of the hosts
microflora
narrow-spectrum drugs also
decreases the likelihood that
organisms will develop drug
resistance.
 Modes of Action
INHIBITION OF CELL WALL
SYNTHESIS
Antibiotics such as penicillin and cephalosporin
contain a chemical structure called a b-lactam
ring, which attaches to the enzymes that cross-
link peptidoglycans. By interfering with the cross-
linking of tetrapeptides, these antibiotics prevent
cell wall synthesis

Fungi and Archaea, whose cell walls lack

peptidoglycan, are unaffected by these antibiotics
 DISRUPTION OF CELL MEMBRANE
FUNCTION

Certain polypeptide antibiotics, such as

polymyxins, act as detergents and distort
bacterial cell membranes, probably by
binding to phospholipids in the membrane

These antibiotics are especially effective

against Gramnegative bacteria, which have
an outer membrane rich in phospholipids
 INHIBITION OF NUCLEIC ACID
SYNTHESIS

Differences between the enzymes used by

bacterial and animal cells to synthesize
nucleic acids provide a means for selective
action of antimicrobial agents. Antibiotics of
the rifamycin family bind to a bacterial RNA
polymerase and inhibit RNA synthesis
 ACTION AS ANTIMETABOLITES

Antimetabolites are substances that affect the

utilization of metabolites and therefore prevent a cell
from carrying out necessary metabolic reactions.
Antimetabolites function in two ways:
(1)by competitively inhibiting enzymes and
(2) by being erroneously incorporated into important
molecules such as nucleic acids.
 PENICILLIN-FAMILY
ANTIBIOTICS
All penicillin-family antibiotics have a
beta-lactam ring. For this reason they
are also called the betalactam
antibiotics.
 Mechanism of Action
To be effective the beta-lactam
penicillin must:
1) Penetrate the cell layers.
2) Keep its beta-lactam ring intact.
3) Bind to the transpeptidase
(penicillin-binding protein).
 Types of Penicillin
1) Penicillin G: This is the original penicillin discovered by Fleming,

2) Aminopenicillins: These penicillins offer better coverage of

gram-negative bacteria

3) Penicillinase-resistant penicillins: This group is useful

against beta-lactamase

4) Anti-Pseudomonal penicillins (including the

carboxypemcillins, ureidopenicillins, and monobactams): This
group offers even wider coverage against gram negative bacteria

5) Cephalosporins: This is a widely used group of antibiotics

that have a beta-lactam ring, are resistant to beta-lactamase, and
cover a broad spectrum of grampositive and gram-negative
bacteria.
 The Resistance of
Microorganisms
The Resistance of
Microorganisms
1. Alteration of Targets.
2. Alteration of Membrane
Permeability.
3. Development of Enzymes.
4. Alteration of an Enzyme.
5. Alteration of a Metabolic
Pathway.