Definition, types; mutation, gene transfer, prevention of drug resistance.
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ANTIBIOTICS RESISTANCE
Resistance is defined as the unresponsiveness of a microorganism to antibiotic.
The resistance may be natural or acquired.
Natural resistance
Natural resistance is genetically determined, for example, normally gram negative bacilli are not affected by penicillin G.
This type of resistance does not pose significant clinical problem.
Acquired resistance
- It is the development of resistance by an organism (which was sensitive before) due to the use of an AMA over a period of time.
- This can happen with any microbe and is a major clinical problem.
- However, resistance development is dependent on the microorganism as well as drug.
- Gonococci quickly developed resistance to sulfonamide, but only slowly and low grade resistance to penicillin.
Resistance may be developed by mutation or gene transfer.
Mutation : It is stable and heritable genetic change that occurs spontaneously and randomly among microorganisms.
It is not induced by AMA.
Mutation and resistance may be :
i) Single step : A single gene mutation may confer high degree if resistance; emerges rapidly, e.g. enterococci to streptomycin, E.coli and Staphylococci to rifampin.
ii) Multistep : A number of gene modifications are involved; sensitivity decreases gradually in a stepwise manner.
Resistance to erythromycin, Tetracyclines and Chloramphenicol is developed by many organisms in this manner.
Sometimes mutational acquisition of resistance is accompanied by decrease in virulence, e.g. certain rifampin resistant Staphylococci and low grade penicillin resistant gonococci have decreased virulence.
Gene transfer :
Infectious resistance from one organism to another can occur by :
i) Conjugation : It is the transfer of genetic material between bacteria during mating, e.g. enterococcal and Staphylococcus aureus resistance to vancomycin.
ii) Transduction : It is the transfer of DNA from one bacteria to another through bacteriophage, e.g. transfer of Antibiotics resistance among the strains of S.aureus.
iii) Transformation : It is transfer of genetic material through naked DNA, e.g. Penicillin resistance in pneumococci.
Resistance bacteria 》》 Release naked DNA into the environment 》》 Taken up by sensitive bacteria that develop resistance to AMAs
■ Resistant organism can be :
a) Drug tolerant : Loss of affinity of the target biomolecule of the microorganism for a particular AMA, e.g. resistant Staph. aureus and E. coli develop a RNA polymerase that does not bind rifampin.
b) Drug destroying : The resistant microbe elaborates an enzyme which inactivates the drug,
e.g.
(i) beta-lactamase are produced by Staphylococci, Haemophilus, Gonococci etc which inactivate penicillin G.
(ii) Chloramphenicol acetyl transferase is acquired by resistant E. coli, H. influenzae.
c) Cross resistance : Organisms that develop resistance to an AMA may also show resistance to other chemically related AMAs.
The cross resistance among AMAs could either be one way or two way. The cross resistance among tetracyclines and sulfonamides is usually two way.
Tetracycline 》《 Doxycycline ( Tetracycline)
Sulphadiazine 》《 Sulphadoxine (Sulphonamides)
Gentamycin 》 Streptomycin
The one way resistance is seen between gentamycin and Streptomycin. The Gentamycin resistant organisms may be resistant to Streptomycin also.
But many Streptomycin resistant organisms still respond ti Gentamycin.
Also read something more about Antibiotics: 👇
Antibiotics • Classification • Antibiotics selection • Problems arise with use of Antibiotics • Why Combination of Antibiotics • Top 10 Antibiotics
e.g.
(i) beta-lactamase are produced by Staphylococci, Haemophilus, Gonococci etc which inactivate penicillin G.
(ii) Chloramphenicol acetyl transferase is acquired by resistant E. coli, H. influenzae.
c) Cross resistance : Organisms that develop resistance to an AMA may also show resistance to other chemically related AMAs.
The cross resistance among AMAs could either be one way or two way. The cross resistance among tetracyclines and sulfonamides is usually two way.
Tetracycline 》《 Doxycycline ( Tetracycline)
Sulphadiazine 》《 Sulphadoxine (Sulphonamides)
Gentamycin 》 Streptomycin
The one way resistance is seen between gentamycin and Streptomycin. The Gentamycin resistant organisms may be resistant to Streptomycin also.
But many Streptomycin resistant organisms still respond ti Gentamycin.
Also read something more about Antibiotics: 👇
Antibiotics • Classification • Antibiotics selection • Problems arise with use of Antibiotics • Why Combination of Antibiotics • Top 10 Antibiotics
Prevention of drug resistance
- No indiscriminate and inadequate or unduly prolonged use of AMAs should be made.
- Prefer rapidly acting and selective AMAs whenever possible; broad spectrum drug should be used only when a specific one cannot be determined or is not suitable.
- Use if combination of AMAs whenever prolonged therapy is undertaken, e.g. tuberculosis, SABE.
- Infection by organisms notorious for developing resistance, e.g. Staph.aureus, E.coli, M.tuberculosis, Proteus etc. must be treated intensively.
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