ANTIMICROBIAL CHEMOTHERAPY: -

 The term chemotherapy was coined by the German

medical researcher Paul Ehrlich to describe the use of
chemical substances to kill pathogenic organisms without
injuring the host.
General properties of antimicrobial agents:-
Selective toxicity:-
 For internal use on antimicrobial drug must have selective
toxicity that is it must harm the microbes without causing
significant damage to the host.
The spectrum of activity:-
 The range of different microbes against which an
antimicrobial agent acts is called it’s spectrum of activity
 Spectrum of activity is two types-
1) Broad spectrum:-
 Those agents that are effective against a great
number of microorganisms from a wide range of
taxonomic groups including both gram positive and
gram negative bacteria are said to have a broad
spectrum of activity.
2) Narrowspectrum:-
 Those that are effective against only a small no. of
microorganisms or a single taxonomic group have a
narrow spectrum of activity.
  A broad spectrum drug is especially useful when a
patient is seriously ill with an infection caused by
an unidentified organisms.
 If the identify of the organism is known a narrow
spectrum drug should be used using such a drug
minimizes the destruction of the host’s microflora
or normal flora, the indigenous microbes that
naturally occur in or on the host that sometimes
compute with and help to destroy infectious
organisms.
MODES OF ACTION:-
Five different modes of action of antimicrobial are discussed
here
1) Inhibition of cell wall synthesis.
2) Disruption of cell membrane function.
3) Inhibition of protein synthesis.
4) Inhibition of nucleic acid synthesis.
5) Action as antimetabolites.
1)Inhibition of cell wall synthesis:-
 Inhibiting cell wall synthesis selectively damages bacterial
and fungal cells.
 Bacterial cells especially gram positive ones have a high
internal osmotic pressure with out a normal sturdy cell
wall, these cell burst when subjected to the low osmotic
pressure of body fluids.
  Antibiotics such as penicillin and cephalosporin contain a
chemical structure called β-lactam ring which attaches to
the enzymes that cross-link peptidoglycans.
 By interfering with the cross-linking of tetra-peptides,
these antibiotics prevent cell wall synthesis.
 Fungi, Archaea whose cell wall lack peptidoglycan are
unaffected by these antibiotics.

2.) 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 membranes, probably
by binding to phospholipids in the membrane with this
distortion the membrane is no longer regulated by
membrane proteins and the cytoplasm and cell substances
are lost.
 These antibiotics are especially effective against gram
negative bacteria which have an outer membrane rich in
phospholipids.
 Polyene antibiotics, such as amphotericin B bind to
particular sterols, present in the membrane of fungal cells.
 Polymyxins do not act on fungi, and polyenes do not act on
bacteria.
3 ) Inhibition of protein synthesis:-
  In all cells, protein synthesis requires not only the
information stored in DNA, plus several kinds of RNA, but
also ribosomes.
 Aminoglycoside antibiotics such as streptomycin derive
their name from the amino acids and glycosidic bonds they
contain.
 They act on the 30S portion of bacterial ribosomes by
interfering with the accurate reading of the mRNA
message i. e, the corporation of the correct amino acids.
 Chloramphenicol and erythromycin act on the 50S portion
of bacterial ribosomes inhibiting the formation of the
growing polypeptide.
4 ) Inhibition of Nucleic acid synthesis:-
 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.
2) By using erroneously incorporated into important
molecules such as nucleic acids.
 Consider sulfanilamide and para amino salicylic acid (PSA)
which are chemically very similar to para amino benzoic
 acid (PABA). They competitively inhibit an enzyme that
acts on PABA many bacteria require PABA in order to
make folic acid which they use in synthesizing nucleic acids
and other metabolic products.
Determining microbial sensitivities to antimicrobial agents:-
 Several methods are their like
1) Disk-diffusion method.
2) Dilution method.
3) Automated method.

Disk-diffusion method:-
In the disk-diffusion method or kirby Bauer method,
a standard quantity of the causative organisms is
uniformly spread over an agar plate. Then several filter
paper disks impregnated with specific concentrations of
selected chemotherapeutic agents are placed on the agar
surface. Finally the culture with the antibiotics disks is
incubated. During incubation each chemotherapeutic
agent diffuses out from the disk in all directions. Agents
with lower molecular weights diffuse faster than those
with higher molecular weights clear areas called zones of
inhibition appear on the anger around disks where the
agents inhibit the organisms.
 A newer version of the diffusion test called an
E(epsilometer) test using a plastic strip containing a
gradient of concentration of antibiotics.
The dilution method:-
The dilution method of testing antibiotics sensitivity
was first performed in tubes of culture broth, it is now
performed in shallow wells on standardized plates.
In this method a constant quantity of microbial
inoculum is introduced into a series of broth cultures
containing decreasing concentration of a
chemotherapeutic agent. After incubation (for 16-20hrs)
the tubes or wells are examined and the lowest
concentration of the agent that prevents visible growth.
This concentration is the minimum inhibitory
concentration (MIC).
Automated methods:-
One tray with small wells into which a measured
quantity of inoculum is automatically dispensed. As many
as 36 organisms from different patients can be inoculated
onto the same tray and that they containing several kinds
of media suitable for identifying members of different
groups of organisms.
Antibacterial agents:-
1) Inhibitors of cell wall synthesis:-
Penicillins, cephalosporins, carbapenems.
 2) Disrupters of cell membrane:-
Polymyxins to treat skin infections caused by
gram negative bacteria such as p seudomonas.
3) Inhibitors of protein synthesis:-
Aminoglycosides, tetracyclines useful at killing
intracellularly infecting bacteria.
Chromophenicol is used to treat typhoid fever,
several rickettsial infections.
4) Inhibitors of nucleic acid synthesis:-
Rifampin produced by streptomyces
Mediterranean and it blocks RNA transcription.
Antifungal agent:-
 Imidazoles and triazoles affect fungal plasma membranes
by disrupting the synthesis of membrane sterols..
 Polyenes family of antibiotics consists of antifungal agents
that contain at least two double bonds.
A) Amphotericin-B-binds to plasma membrane ergosterol
found in fungi.
B) Nystatin -Same mode of action as amphotericin-B but it
also effective against candida yeast infection.
 Flucytosine is a synthetic drug used to treat infections
caused by candida and several other fungi.
Antiviral agent:-
Purine & pyrimidine analogs: -
 Idoxuridine and trifluridine both analogs of thymine are
administrated in eye drops to treat inflammation of the
cornea caused by a herpes virus.
 Vidarabine an analog of adenine has been used effectively
to treat viral encephalitis.
 Ribavirin a synthetic nucleotide analog of guanine blocks
replication of certain viruses.
 Ziduvudine interferes with reverse transcriptase making
DNA from RNA it is used in treating AIDS.
Antiprotozoan agents: -
 Quinine from the bank of the cinchona tree was used
for to treat malaria.
 Metronidazole causes breakage of DNA strands. It is
effective in treating Trichomonas infections.