Antibiotics in clinical practice

2021-06-23 02:58 PM

Antibiotics are substances that even at low concentrations have the effect of inhibiting or killing microorganisms, bacteria, fungi, protozoa, viruses without affecting macrobiotic cells.

Some concepts

In 1928, Fleming discovered the fungus Penicillium notatum to kill Staphylococcus aureus at Saint Marie Hospital. In 1940, a team at Oxford (Flory, Chain and Hartley) purified penicillin and ushered in the era of antibiotics to treat infections. To date, more than 2,000 antibiotics have been identified, but only a few (about 50) of which are used to treat human disease.

According to Meyers, antibiotics are substances that inhibit metabolism, which is initially secreted by living cells, mostly microorganisms, especially Streptomyces’s fungi. But to date, many derivatives of these substances have been obtained after chemical transformations by the semisynthetic route. Some drugs are completely synthesized in the laboratory, called chemotherapeutic agents, eg sulphonamides. Therefore, antibiotics (antibiotica) and chemotherapeutic agents (chemotherapeutic) are twin names of antibiotics, not antagonistic, but historical.

Some antibiotics specifically inhibit the metabolism of bacteria, so they are used to treat bacterial infections such as penicillin, streptomycin. Some antibiotics inhibit the metabolism of both prokaryotes (prokaryotes) and eukaryotes (eukaryotes) such as mitomycin C, so are used for experimental studies and some can be used for cancer treatment (Actinomycin D) ).

Definition: Antibiotics are substances that even at low concentrations have the effect of inhibiting or killing microorganisms (bacteria, fungi, protozoa, viruses) but have no effect on macrobiotic cells (humans). . Each antibiotic only disrupts a certain biological response of the microbial cell and thereby stops the growth.

This article only deals with antibiotics that fight bacteria called antibacterial agents.

There are many types of classification (see also pharmacology).

Sort by a spectrum of effects

Has the advantage of being easy to remember for antibiotic selection? There are two types of antibiotics: broad-spectrum antibiotics and selective-spectrum antibiotics.

Antibiotics with broad-spectrum activity

An antibiotic that is active against many types of bacteria, both Gram-positive and Gram-negative.

Group aminoglycoside: Streptomycin, gentamicin, kanamycin, neomycin, tobramycin, amikacin ...

The tetracycline group.

Phenicol group.

The sulphonamide and trimethoprim groups.

Antibiotic with a selective spectrum of activity

An antibiotic is only effective on one or a few certain types of bacteria, for example:

Derivatives of isonicotinic acid: INH (Rimifon) is only active against
tuberculosis bacteria.

Macrolide group: effective on Gram-positive bacteria and some Gram-negative bacilli, such as erythromycin, spiramycin...

Polymyxin group or nalidixi acid

Only effective against Gram-negative bacilli.

Beta-lactam antibiotics

Penicillin group: Acts on Gram-positive bacteria, degraded by penicillinase, such as penicillin G, penicillin V...

Methicillin group (also called anti-staphylococcal penicillin): Acts on Gram-positive bacteria, not broken down by penicillinase, such as cloxacillin, flucloxacillin, nafcillin...

Penicillin against Pseudomonas: Destroyed by beta-lactamases such as carbenicillin, ticarcillin, azlocillin...

Ampicillin group: Has a broad spectrum of activity, is degraded by penicillinase, such as ampicillin, amoxicillin, mecilinam, pivampicillin...

Group of cephalosporins: Has broad-spectrum activity, is not degraded by penicillinase, divided into 3 (to date) generations, including 1st generation such as cephalothin, cephalexin...; 2nd generation such as cefamandole, cefuroxime, cefoxitin...; 3rd generation such as cefotaxime, ceftriaxone, ceftazidime, latamoxef...

Sort by mode of action

If classified according to the mode of action, people divide antibiotics into 2 types: Antibiotics with bacteriostatic effects (bacteriostatic) and antibiotics with bactericidal effects (bactericidal); but in reality there is no clear boundary for this distinction. Because some bacteriostatic antibiotics at higher concentrations have a bactericidal effect. This depends on the type and number of bacteria, on the stage of growth, on the growth rate of the bacteria, on the medium and on the concentration of antibiotics.

Some drugs have bacteriostatic effects such as: fusidic acid, nalidixic acid, clindamycin and lincomycin, erythromycin, nitrofurantoin, sulfamic, tetracycline, trimethoprim.

Drugs that inhibit the growth of bacteria; however, to destroy and kill bacteria, it also needs the participation of the human body's defence system (macrophages, antibodies...). Bacteriostatic drugs have no effect on bacterial cells at rest, so it is required that antibiotic concentrations must always be maintained at a level sufficient to inhibit the growth of bacteria at the site of infection; Patients only recover from the disease when the body's immune system is capable of eliminating the suppressed bacteria from the body.

Some drugs have a bactericidal effect such as polymyxin, aminoglycoside, cephalosporin, Fosfomycin, 5-nitroimidazole, penicillin, rifampicin, vancomycin

The drug has a bactericidal effect, that is, irreversibly disrupts the function of bacterial cells and leads to death. The only polymyxin has an absolute bactericidal effect because its mechanism of action is similar to that of a detergent, destroying the selective osmotic function of the plasma membrane; while other drugs have a bactericidal effect only on degenerative bactericides, for example, penicillin inhibits wall biosynthesis. The bactericidal kinetics depends on the concentration of the drug.

Mechanism of action of antibiotics

After entering the cell, the antibiotic delivered to the target will work by:

inhibition of bacterial cell wall biosynthesis: The bacteria produced will not have a wall and are therefore easily destroyed, for example, beta-lactam antibiotics, vancomycin.

Disruption of plasma membrane function, especially selective osmosis function, causing components (ions) inside the cell to escape, eg polymyxin.

Inhibition of protein biosynthesis: The point of action is the bacterial 70S ribosome and as a result protein molecule are neither formed nor biologically active.

In the 30S subunit: For example, streptomycin interferes with messenger RNA activity or tetracyclines prevent activated transporter RNAs from binding to the ribosome.

In the 50S subunit: Like chloramphenicol, erythromycin interferes with the binding of amino acids by binding to the enzyme peptidyl transferase.

Inhibition of nucleic acid biosynthesis: Includes

Inhibits the replication of DNA to create daughter DNA, such as quinolones inhibit the enzyme gyrase, making the DNA molecule unable to open the helix.

Inhibits RNA biosynthesis such as rifampicin, by binding to DNA-dependent RNA polymerase.

Inhibition of biosynthesis of metabolites necessary for cells, for example, sulphonamides and trimethoprim inhibit the metabolism to produce folic acid - a coenzyme required for the synthesis of some amino acids and purines, pyrimidines.

Therefore, when combining antibiotics in treatment, people often use antibiotics with different targets (mechanisms of action) to increase the ability to kill a bacterial species.