NAJRAN UNIVERSITY
College of Medicine
Microbiology &Immunology Course
Lecture No. 7
By
Dr. Ahmed Morad Asaad
Associate Professor of Microbiology
ANTIMICROBIAL AGENTS
DEFINITIONS :
Antibiotic: An antimicrobial agent produced by a living
organism and can kill or inhibit the growth of other
organisms.
Chemotherapeutic agents: Synthetic substances (drugs)
with similar antimicrobial activities to that of antibiotics.
Bactericidal agents: Substances (drugs), which kill and
destroy bacteria.
Bacteriostatic agents: Substances (drugs), which inhibit
the growth and multiplication of bacteria.
Properties of an ideal antimicrobial agent:
1. Selective toxicity: The antimicrobial agent must be
harmful to bacteria but relatively harmless (non-toxic) to the
host cells.
2. Broad spectrum: it should affect a variety of bacteria
(both Gram positive and Gram negative).
3. Bactericidal agents (which kill and destroy bacteria) are
better than bacteriostatic agents (which inhibit the growth
and multiplication of bacteria).
4. It should be diffusible into distant body areas with slow
rate of excretion.
5. Bacteria (target cells) do not develop resistance to it.
Mechanism of action of antimicrobial agents:
1- Inhibition of cell wall synthesis; e.g. penicillin and cephalosporins.
2- Inhibition of cell membrane function; e.g. polymyxins,
amphotericin-B, nystatin and colistin.
3- Inhibition of protein synthesis leading to inhibition of cell growth., e.g
chloramphenicol, streptomycin, tetracyclines, griseofulvin and
aminoglycosides (Amikin, Gentamicin).
4. Inhibition of nucleic acid synthesis:
a. RNA inhibition; by inhibiting RNA polymerase of bacteria,
(Rifampicin).
b. DNA inhibition: nalidixic acid, novobiocin, metronidazole and
quinolones.
5- Competitive inhibition; e.g. sulphonamides compete with
para- aminobenzoic acid (PABA) for the active site of the enzyme
involved in folic acid synthesis.
Choice of Antimicrobial Agent
1) In-vitro tests of bacterial sensitivity to antibiotics:
a. Disc diffusion method: A culture medium is inoculated with
the organism. Discs impregnated with different antibiotics are
placed and the plate is incubated at 37ºC for 24 hrs. The
degree of inhibition by the antibiotic is measured by the
diameter of the zone of inhibition (the more the zone of
inhibition, the more the sensitivity).
b. Dilution method: Serial dilutions of the antibiotic are
inoculated with the organism to determine the minimal
inhibitory concentration (MIC), which is the lowest
concentration of the antibiotic that inhibits growth of the
organism.
2) Empirical use of antibiotics
Using antibiotics without in-vitro tests is indicated in the
following conditions :
1- In closed lesions with no available sample (e.g. brain
abscess).
2- While waiting for the result of in-vitro sensitivity test.
Antimicrobial Drug Combinations
This is indicated in the following conditions:
1. In severe infections of unknown (undiagnosed) organism.
2. For complete eradication of the organism to avoid occurrence
of complications.
3 In severe mixed infections with organisms that have different
drug sensitivities.
4. To avoid development of resistant strains especially with
prolonged course of treatment, e.g. in tuberculous infections.
5. Synergism: The combined effect of a pair of antimicrobial
agents is greater than the sum of their independent activities,
E.g., use of penicillin and genatamicin in treatment of
enterococcal endocarditis
Complications of antimicrobial chemotherapy
1. Toxicity :
a. Streptomycin is toxic to the 8 th cranial nerve.
b. Chloramphenicol may cause bone marrow depression
(aplasia).
c. Aminoglycosides (gentamicin, amikacin, ..) are nephrotoxic.
d. Tetracyclines may cause teeth deformity and liver damage.
2. Hypersensitivity : Some antimicrobial agents act as haptens.
When they bind to host macromolecules they become antigenic
resulting in one of the hypersensitivity reactions
3. Superinfection:
During treatment with a broad -spectrum antibiotic, susceptible
members of normal flora at different sites of the body are killed.
This will result in a biological imbalance. Bacteria resistant to the
antibiotic used may cause a superinfection (i.e. an infection on
top of antibiotic administration), e.g.
1- Candida may cause oral thrush or vaginitis.
2- Pseudomonas and Staphylococci may cause wound
infections in hospitalized patients.
3- Gram negative bacilli (Proteus, Pseudomonas, E. coli) may
cause genital or respiratory tract infections.
4- Clostridium defficile and Staphylococci may cause
enterocolitis.
4. Masking the diagnosis:
Early administration of antibiotics may decrease the antigenic
mass needed to stimulate antibody formation. This will interfere
with serological diagnosis. e.g. typhoid fever.
5. Development of resistant strains:
Resistant strains may emerge due to:
- Selection of bacteria which are naturally resistant to the
antibiotic given.
- Genetic variations (e.g. mutation or gene transfer by
conjugation, transformation, transduction or lysogenic
conversion).
The organism may acquire resistance due to one of the following
mechanisms:
- Production of specific enzymes to inactivate the antibiotic, e.g.
Staphylococci produce P-lactamase enzyme to inactivate
penicillin and cephalosporins.
- Decreased permeability to antibiotics to prevent it s entrance.
e.g. Streptococci are resistant to aminoglycosides by this
mechanism.
- Alteration of target sites or receptors for the drug action, e.g.
organisms resistant to erythromycin and chloramphenicol have
an altered receptor site in the 50S component of their
ribosomes.
- Development of alternative metabolic pathway to bypass the
pathway which is inhibited by the drug, e.g. organisms resistant
to sulphonamide utilize the folic acid of the surrounding media
(sparing ) with no need for PABA.
Limitation of Drug Resistance
Emergence of drug resistance in infections may be minimized in
the following ways:
1. Maintain high levels of the drug in the tissue to inhibit both the
original population and first step mutants.
2. Simultaneously administer two drugs, each of which delays
the emergence of mutants resistant to the other drug.
3. Avoid exposure of micro-organisms to a particularly valuable
drug by restricting its use
Chemoprophylaxis
It is the administration of antimicrobial drugs to prevent infection
i.e. before the development of a disease.
Examples:
1- The injection of penicillin G, once every 3-4 week to prevent
reinfection with group A β-hemolytic streptococci in
rheumatic fever.
2- Prevention of meningitis by eradicating the meningococci
with rifampin.
3- Prevention of syphilis by the injection of penicillin G.
4- Prevention of cholera by oral administration of tetracyclines.
5- Prevention of recurrent urinary tract infection by oral intake
of nitrofurantion.
6- In major surgical procedure, the administration of a broad
spectrum bactericidal drug from just before until after the
procedure, has been found effective.