May 29, 2024
Intrinsic Resistance
Acquired Resistance
Examples Of Intrinsic Resistance
Antimicrobial agents can be classified according to several characteristics: Site of action (such as the ribosome or cell wall); Chemical structure (such as B-lactams, quinolones); It works on the ribosome, the cell wall, or the nucleic acid. Therefore, the second method of classification is where the medicine is acting.
The way in which it works (bactericidal or bacteriostatic
Chemical class |
Site of action |
Mode of action |
Comments |
B-lactams
|
Cell wall |
Bactericidal |
|
Carbapenems |
Cell wall |
Bactericidal |
|
Glycopeptides
|
Cell wall |
Bactericidal |
|
Aminoglycosides
|
Ribosome |
Bactericidal |
|
Macrolides |
Ribosome |
Bacteriostatic |
|
Trimethoprim |
Dihydrofolate reductase |
Bacteriostatic |
|
Sulfamethoxazole |
Di-hydropteroate synthetase |
Bacteriostatic |
|
Quinolones |
DNA topoisomerase II, gyrase |
Bacteriostatic |
|
Lincosamides: Clindamycin |
Ribosome |
Bacteriostatic |
|
Oxazolidinones: Linezolid |
Ribosome |
Bacteriostatic |
|
Nitroimidazoles: Metronidazole |
Directly damages DNA and proteins through the formation of radicals. |
Bacteriocidal |
|
With the exception of the last medication, which is bactericidal, all of these are bacteriostatic. Penicillin, cephalosporin, carbapenem, vancomycin, and aminoglycoside were all categorized as bactericidal in earlier systems.
Macrolides that act on the ribosome include azithromycin and clarithromycin. Because tablets have a good oral absorption rate, they are administered that way. However, they can cause gastrointestinal adverse effects such as nausea, vomiting, and discomfort in the abdomen.
As a teratogenic drug, trimethoprim and sulfamethoxazole (cotrimoxazole combination of trimethoprim and sulfamethoxazole) cannot be used during pregnancy, especially in the first trimester, due to its inhibition of dihydrofolate reductase. Quinolones are prescribed for infections of the upper respiratory tract. One medication for staph infection is claridamycin. Due of its excellent tissue penetration, the oral version is recommended.
Nitrimidazole should not be used while pregnant. Linezolid is prescribed for MRSA infections, particularly if the patient is not responding to conventional antibiotics.
Also Read: Platelet Activation, Adhesion, And Formation Of Platelet Plug
Agent Expected spectrum of activity Penicillin VBenzyl-penicillin Alpha - hemolytic streptococci S. pneumoniaS. pyogenes Amoxicillin Streptococcal, enterococciSome Gram-negative cover Flucloxacillin Methicillin-sensitive S. aureus Amoxicillin with clavulanic acidPiperacillin with tazobactam Broad spectrum Gram-positive, Gram-negative, and anaerobic cover, but not MRSA
Long-acting penicillins often include benzothenepenicillin and benzoylpenicillin. That can also be administered once every 15 days or once a month. The best medication for pseudomonas would be an aminoglycoside combined with piperacillin, monobactam, or tazobactam.
Commonly used cephalosporins Expected spectrum of activity Cefuroxime (2nd generation) Cefotaxime (3rd generation) Ceftriaxone (3rd generation) Broad spectrum Gram-positive and gram-negative cover, but not MRSA Commonly used Carbapenems Meropenem Ertapenem
Carbapenems are a good medication of choice when we wish to utilize antibiotics with broad-spectrum action for both gram-positive and gram-negative bacteria. When treating patients with broad spectrum infections, imipenem, meropenem, ertapenem, and thiopenem are utilized in intensive care units rather than as first medications.
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By using the minimal inhibitory concentration approach, we can determine the smallest concentration of antibiotic needed to stop the growth of bacteria. The broth dilution approach yields the most precise results for this. The tested antimicrobial is serially diluted and added to tubes holding a broth medium in this test.
Next, a standardized inoculum containing the target organism is introduced. Following an incubation period, the tubes are checked for the existence of bacterial growth. The antibiotic under test has a minimum inhibitory concentration (MIC) that is determined by the first dilution at which no growth is observed.
These are distinct test tubes with different antimicrobial agent concentrations in each test tube. In the first, it is 0.125, followed by 0.25, 0.5, 1, 2, 4, 8, 16, and so forth. This indicates that the value of antimicrobial agents has increased. We are adding a standardized bacterial inoculum to each of these. This is when inhibition is most noticeable. There was no inhibition below this. Above everything, though, is inhibition.
The lowest concentration of antibiotics that can stop bacterial growth is 2 ug. It takes a lot of time and work, and frequent use in a diagnostic lab is not feasible. It is necessary to take several antibiotics, several inoculants, and various dosages of each antibiotic.
It is the cornerstone of the majority of automated susceptibility testing techniques. Antimicrobial disc diffusion testing is an alternate technique that involves uniformly inoculating a particular testing media with a standardized suspension of the test organism.
On the medium, a variety of paper discs with predetermined concentrations of antimicrobials are placed. Depending on how much the antibiotic can stop bacteria from growing, it will diffuse from the disc into the medium. This will result in a gradient of concentration, with the highest concentration occurring immediately surrounding the disc.
The more they impede bacterial growth, the more diffused it becomes. It will spread less the less they prevent bacterial development. The microorganism's effective dose will be the paper that causes the greatest amount of diffusion.
This zone needs to match or exceed a specific diameter, which changes depending on the organism and antibiotic. This zone is then considered sensitive.Extensive databases of susceptibility breakpoints are necessary for the interpretation of these results. A third technique, called the E-test, makes use of plastic strips coated with the antimicrobial under test, creating a gradient in concentration along the strip.
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This is an illustration of intrinsic resistance, which derives from characteristics shared by all organism strains. This indicates that the organism has altered or modified its strain; in such case, inherent resistance is present. They are rendered prior to the effects of an antibiotic due to characteristics of the cell wall or metabolis
A bacterial organism is said to have acquired resistance if it develops resistance to an antimicrobial agent or class to which it was previously susceptible.A novel mutation or the spread of resistance from other organisms could be to blame for this. A spontaneous mutation that arises at random and confers resistance to an antimicrobial drug is known as chromosomal resistance.
Organism Intrinsic antimicrobial resistances Mechanism Gram-negative organisms Vancomycin Agent unable to penetrate the outer membrane of cell wall Aerobic bacteria Metronidazole Aerobic metabolism is unable to reduce the agent to its active form Anaerobic bacteria Aminoglycoside Active uptake of agents dependent on oxidative metabolism
Mechanism Of Horizontal Gene Transfer
Mechanism | Genetic element transfer | Method of transfer |
Transformation | Free genetic material from lysed organisms | Uptake of exogenous DNA from the environment |
Conjugation | Mobile genetic elements, e.g., plasmids or transposons | Via direct cell-to-cell contact or through specific cell bridges (pili) |
Transduction | Mobile genetic elements, e.g., plasmids or transposons | Introduction of foreign genetic material via viral (phage) vector |
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