Chemotherapeutic agents/ Antimicrobial Agents

Chemotherapeutic agents are chemical substances used in the treatment of infectious

diseases. Their mode of action is to interfere with microbial metabolism, thereby producing
a bacteriostatic or bactericidal effect on the microorganisms, without producing a like
effect in host cells. Chemotherapeutic agents act on a number of cellular targets. Their
mechanisms of action include inhibition of cell-wall synthesis, inhibition of protein
synthesis, inhibition of nucleic acid synthesis, disruption of the cell membrane, and
inhibition of folic acid synthesis. These drugs can be separated into two categories :
1. Antibiotics are synthesized and secreted by some true bacteria, actinomycetes, and
fungi that destroy or inhibit the growth of other microorganisms. Today, some antibiotics
are laboratory synthesized or modified; however, their origins are living cells.
2. Synthetic drugs are synthesized in the laboratory. The specific mechanism of action
varies among different drugs, and the short-term or long-term use of many drugs can
produce systemic side effects in the host.
How do antibiotics work?
All antibiotics have the common property of interfering in some way with a normal, critical
function of the target bacterial cell. The most commonly used antibiotics exert
their effect by one of the following methods:
1. Inhibition of cell wall synthesis (group I)
2. Disruption of cell membranes (group II)
3. Interference with protein synthesis (group III)
4. Interference with nucleic acid synthesis (group IV)
Group I: Inhibitors of cell wall synthesis
The main group which work in this way are the β-lactam antibiotics, so-called because they
contain a β-lactam ring in their structure. Included among this group are the penicillins and
the cephalosporins. They Prevents transpeptidation of the N-acetylmuramic
acids(peptidoglycan), producing a weakened peptidoglycan structure, as the wall weakens,
water enters the cell, leading to swelling and then lysis.
Group II: Antibiotics that disrupt cell membranes
Polymyxins are a class of antibiotic that act by disrupting the phospholipids of the
cytoplasmic membrane and causing leakage of cell contents. Produced naturally by a
species of Bacillus, polymyxins are effective against pseudomonad infections of wounds and
burns, often in combination with bacitracin and neomycin.
Group III: Inhibitors of protein synthesis
Antibiotics that act by affecting protein synthesis generally have a relatively broad
spectrum of action. Streptomycin, gentamicin, kanamycin, tetracyclines and neomycin are
some example of this group of antibiotics. These antibiotics have an affinity for bacterial
ribosomes, causing misreading of codons on mRNA, thereby interfering with protein
synthesis, ultimately stops the growth of bacteria.
Group IV: Inhibitors of nucleic acid synthesis
Rifampin belongs to a group of agents called rifamycin. It acts by inhibiting the enzyme
RNA polymerase, thereby preventing the production of mRNA. Rifampin is used against the
mycobacteria that cause tuberculosis, an application for which its ability to penetrate
tissues make it well suited. When used in high doses, it has the unusual side effect of
turning secretions such as tears, sweat and saliva, as well as the skin, an orange red color.
Antimicrobial resistance
 Antimicrobial resistance occurs when microbes evolve mechanisms that protect
them from the effects of antimicrobials. The term antibiotic resistance is a subset of
AMR, as it applies to bacteria that become resistant to antibiotics. It happens when
germs like bacteria and fungi develop the ability to defeat the drugs designed to kill
them.

How does antibiotic resistance work?

Resistance
Mechanisms
(Defense
Strategies) Description

Restrict access of Germs restrict access by changing the entryways or limiting the number of
the antibiotic entryways.
Example: Gram-negative bacteria have an outer layer (membrane) that
protects them from their environment. These bacteria can use this
membrane to selectively keep antibiotic drugs from entering.

Get rid of the Germs get rid of antibiotics using pumps in their cell walls to remove antibiotic
antibiotic drugs that enter the cell.
Example: Some Pseudomonas aeruginosa bacteria can produce pumps to get rid of
several different important antibiotic drugs, including fluoroquinolones, beta-
lactams, chloramphenicol, and trimethoprim.
 Resistance
Mechanisms
(Defense
Strategies) Description

Change or destroy Germs change or destroy the antibiotics with enzymes, proteins that break down
the antibiotic the drug.
Example: Klebsiella pneumoniae bacteria produce enzymes called carbapenemases,
which break down carbapenem drugs and most other beta-lactam drugs

Bypass the effects Germs develop new cell processes that avoid using the antibiotic’s target. 
of the antibiotic
Example: Some Staphylococcus aureus bacteria can bypass the drug effects of
trimethoprim

Change the targets Many antibiotic drugs are designed to single out and destroy specific parts (or
for the antibiotic targets) of a bacterium. Germs change the antibiotic’s target so the drug can no
longer fit and do its job.
Example: Escherichia coli bacteria with the mcr-1 gene can add a compound to the
outside of the cell wall so that the drug colistin cannot latch onto it.

 To prevent and control the spread of antibiotic resistance, individuals can:

 Only use antibiotics when prescribed by a certified health professional.

 Never demand antibiotics if your health worker says you don’t need them.
 Always follow your health worker’s advice when using antibiotics.
 Never share or use leftover antibiotics.
 Prevent infections by regularly washing hands, preparing food hygienically,
avoiding close contact with sick people, practicing safer sex, and keeping
vaccinations up to date.
 Prepare food hygienically, following the WHO Five Keys to Safer Food (keep clean,
separate raw and cooked, cook thoroughly, keep food at safe temperatures, use safe
water and raw materials) and choose foods that have been produced without the
use of antibiotics for growth promotion or disease prevention in healthy animals.