Antibiotics are the substances which are obtained from living organism but can stop or inhibit the activities or growth of other microorganism in high dilutions. The history of antibiotics usage is very earlier. It is thought that antibiotic concept came into being when Jhon Tendal first described the antagonistic activity of fungi against certain bacteria in England in 1875. Antibiosis was first described in bacteria in 1877 when Louis Pasteur and Robert Koch observed that air borne spores of the Bacillus can inhibit the growth of Bacillus anthracis. But it was in 1928 when the Allexander Fleming saw the antibiosis of genus penicillum against bacteria. At the last, Florey and Chain were succeeded in obtaining the first penicillin , named the penicillin G, in 1942 and so from that time the antibiotic flow started in the world. Later on, the work progressed and new synthetic antibiotic came into the practice. The first synthetic compound was sulfonamide which was developed by the Domagk in 1932 in Bayer laboratories of the Germany.
We use antibiotics for everything from treating
viral infections against which antibiotics are useless to promoting the growth
of livestock to curing acne. People often demand antibiotics from their doctors
even in the absence of proof of a bacterial infection. And people often neglect
to complete a full course of antibiotics once it has been prescribed. Due to
the over usage of antibiotic in food producing animals, therapeutic efficacy of
certain antibiotics started to decrease and a specific term was used for this
which is called resistance. Resistance is the reduction in
effectiveness of a drug in curing a disease or improving a patient's symptoms. According
to the European commission report in 2005, it is estimated that over 10 million
tons of antibiotic had been released in the biosphere during the last 60 years.
This has exerted a very strong selective pressure for the appearance of
resistance.
Antibiotic resistance was first discovered in the 1940’s when
it was identified in a microorganism called Staphylococcus
aureus which is resistant to
penicillin. As resistant
strains of bacteria emerge, they have easy passage to humans—right though the
grocery store. Antimicrobial use in agriculture can also compromise human
therapies when bacteria develop cross-resistance—when their resistance to one
drug also makes them resistant to other, related drugs. Resistance is of two types, the first one is,
Innate resistance and the second one is Acquired resistance. In innate
resistance, the
principles of Darwinian evolution act on bacteria with inherent resistance.
Those bacteria that resist an antibiotic's effects are better suited to survive
in an environment that contains the antibiotic. In the case of inherent
resistance and vertical evolution, the genes that confer resistance are found
on bacterial chromosomes and are transferred to the bacterial progeny every
time the cell divides. Bacteria may
begin life resistant to a particular antibiotic. Like Gram negative bacteria are inherently resistant to Penicillin
and Vancomycin antibiotics. Bacteria that don’t begin life resistant to a
certain antibiotic can acquire that resistance. In the case of vertical evolution
and inherent resistance, mutations occur on chromosomes and are then selected
for an environment where resistance increases fitness. In the case of
horizontal evolution, genes pass from a resistant strain to a nonresistant
strain, conferring resistance on the latter. For acquired resistance there are two types of mechanisms through
which the organism become acquired to resistance. The first one is mutation in
the genetic make up of the organism and then these mutations are selected for
the resistance. In this type of resistance, any insertion deletion or substitution
of the nucleotide take place which is responsible for the resistance. The
second mechanism through which the acquired resistance developed is transduction,
transformation or conjugation. In transduction simply a bacteriophage virus
unintentionally take the DNA of the resistant bacteria and transmit it to the
other bacteria. In transformation simply a bacteria rupture and transmit its
genetic matrial to the next bacteria for its reproduction. In conjugation, a
bridge is developed between two bacteria and genetic material flows from one
bacteria to the other.
Causes
of Resistance
There are many causes of resistance.
The first cause of the resistance development of
bacteria against a specific antibiotic is the improper diagnosis of the disease.
If a patient is not properly diagnosed, the technician give more than one
antibiotics at a time and this can leads to the development of the resistance
against a specific antibiotic to which it was earlier sensitive.
The second and the most important cause of the
antibiotic resistance is the transmission of DNA material (plasmid) from one
organism to the other without the offspring of that one. This is also called horizental
gene transfer.
The third cause of the development of the
antibiotic resistance is the over usage of the broad spectrum antibiotics. The
use of the narrow spectrum antibiotic is preferred than the broad spectrum
antibiotics. If we use the broad spectrum antibiotics the chance to survival of
the sensitive bacteria increases and hence bacterial resistance to an
antibiotic occurs.
The fourth cause of the bacterial resistance to
an antibiotic is the unnecessary prescription. If a person takes some medicine
without a need, the chance to an antibiotic resistance increases. Similarly if
a patient suffering from one disease and he take another antibiotic without
having an effect on the organism of the disease, the chances of antibiotic
resistance increases.
The fifth cause of the antibiotic resistance is
taking of lower dosage of an antibiotic than the therapeutic dosage. This leads
to the development of resistance.
The sixth cause of antibiotic resistance
development is the addition of antibiotics into the livestock feed and poultry
feed as a daily ingredient or regular ingredient of the feed. This is the worst
risk factor in the development of antibiotic resistance.
Some of the
many mechanisms of resistance are indicated schematically in the following
diagram
There
are different mechanisms through which bacteria get resistance to an
antibiotic. The first mechanism is the change in the permeability of the
membrane. There are porin channels through which drug molecule get entrance in
to the cell. Some time the protein of these channels becomes adopted and the
entrance of the drug molecule into the cell decreases and hence the resistance
is developed. The second mechanism for the development of the resistance is the
development of the certain types of the enzymes. When a drug molecule enters
into the cell, the developed enzymes degrade the drug molecule and the resistance
becomes developed. The examples of such enzymes are the Betalactamases against penicillin’s
and cephalosporins. The third mechanism for the development of the resistance
is the change in the target protein. Target protein are those protein to which
drug molecule binds and produce there pharmacological effect. Change in the target
protein molecules means that no effect of the drug and hence resistance. The
fourth mechanism of the drug resistance is the development of the e-flux system
with repeated exposure. Some time when a drug get entry into the cell, the cell
develops a pump system which pushes the drug molecule out of the cell and this
is called e-flux system which is also a mechanism for the resistance.
For the prevention of the resistance to
antibiotics, the following measure should be taken. When a person or an animal
become sick it should be checked by the expert physician because only the
expert physician will properly diagnose the disease. The antibiotic used in the
treatment will only be based on the local pattern. No foreign antibiotics and
vaccines should be used because it is the main cause of the resistance. Proper
dose of the antibiotic should be taken. Dose lower than the normal is also the
main cause of the resistance. Misuse of the broad spectrum antibiotic should be
avoided. Narrow spectrum antibiotics would be preferred over the broad spectrum
antibiotics. During surgery appropriate dose of the antibiotic should be used
for the prophylactic purpose (prevention of the infection). Proper antiseptic
protocol will also decrease the usage of the antibiotics. For the diagnosis of
the disease some laboratory test should be performed for the isolation and
detection of the organism. At the last development of the new antibiotics
should be ensured which is based on the local pattern.
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