Generality
Beta-lactams (or β-lactams) constitute a large family of antibiotics, comprising numerous molecules that share the central nucleus at the base of their chemical structure: l "beta-lactam ring, also known more simply as beta-lactam.
The beta-lactam ring - besides constituting the central nucleus of this class of antibiotics - is also the pharmacophore of these molecules, that is, it is the group that confers the antibacterial properties typical of these drugs.
Classes of beta-lactam antibiotics
Within the large family of beta-lactams we find four classes of antibiotics, the penicillins, the cephalosporins, i carbapenems and i monobactams.
The main characteristics of these drugs will be briefly illustrated below.
Penicillins
Penicillins are antibiotics of natural origin, as they derive from a fungus (ie, a fungus).
More precisely, the progenitors of this class of antibiotics - the penicillin G (or benzylpenicillin) and the penicillin V (or phenoxymethylpenicillin) - were first isolated from cultures of Penicillium notatum (a mold now known as Penicillium chrysogenum).
The discovery of penicillin is attributed to Alexander Fleming who, in 1928, observed how the colonies of Penicillium notatum were able to inhibit bacterial growth.
However, benzylpenicillin and phenoxymethylpenicillin were only isolated ten years later by a group of British chemists.
From that moment on, the great development of research in the field of penicillins began, in an attempt to find new and increasingly safe and effective compounds.
Thousands of new molecules were discovered and synthesized, some of which are still used in therapy today.
Penicillins are antibiotics with bactericidal action, that is, they are able to kill bacterial cells.
Among the many molecules belonging to this great class, we remember ampicillin, amoxicillin, methicillin and oxacillin.
Cephalosporins
Cephalosporins - like penicillins - are also antibiotics of natural origin.
The molecule considered the progenitor of this class of drugs - the cephalosporin C - was discovered by the Italian doctor Giuseppe Brotzu of the University of Cagliari.
Over the years, numerous cephalosporins have been developed with increased activity compared to their natural precursor, thus obtaining more effective drugs with a broader spectrum of action.
Cephalosporins are also bactericidal antibiotics.
Cefazolin, cefalexin, cefuroxime, cefaclor, ceftriaxone, ceftazidime, cefixime and cefpodoxime belong to this class of drugs.
Carbapenems
The progenitor of this class of drugs is the thienamycin, which was first isolated from actinomycete Streptomyces cattleya.
It was discovered that thienamycin was a compound with an "intense antibacterial activity, with a broad spectrum of action" and capable of inhibiting some types of β-lactamases (particular enzymes produced by some bacterial species capable of hydrolyzing beta-lactam and to inactivate the antibiotic).
Since thienamycin was found to be very unstable and difficult to isolate, modifications were made to its structure thus obtaining a more stable semisynthetic first derivative, imipenem.
Meropenem and ertapenem also belong to this class of antibiotics.
Carbapenems are antibiotics with bacteriostatic action, that is, they are not able to kill bacterial cells, but they inhibit their growth.
Monobactami
The only drug belonging to this class of antibiotics is aztreonam.
Aztreonam does not come from natural compounds, but is of completely synthetic origin. It has a spectrum of action restricted to Gram-negative bacteria only and also has the ability to inactivate some types of β-lactamases.
Mechanism of action
All beta-lactam antibiotics act by interfering with the synthesis of the bacterial cell wall, i.e. they interfere with the synthesis of peptidoglycan.
Peptidoglycan is a polymer consisting of parallel chains of nitrogenous carbohydrates, joined together by cross-links between amino acid residues.
These bonds are formed by particular enzymes belonging to the peptidases family (carboxypeptidases, transpeptidases and endopeptidases).
Beta-lactam antibiotics bind to these peptidases preventing the formation of the aforementioned transverse bonds; in this way, weak areas are formed inside the peptidoglycan which lead to the lysis and death of the bacterial cell.
Resistance to beta-lactam antibiotics
Some bacterial species are resistant to beta-lactam antibiotics because they synthesize particular enzymes (le β-lactamase) able to hydrolyze the beta-lactam ring; in so doing, they inactivate the antibiotic, preventing it from performing its function.
To remedy this resistance problem, beta-lactam antibiotics can be administered together with other called compounds β-lactamase inhibitors which - as the name implies - inhibit the activity of these enzymes.
Examples of these inhibitors are the "clavulanic acid which is often found in association with amoxicillin (as, for example, in the medicine Clavulin®), the sulbactam which is found in combination with ampicillin (as, for example, in the medicine Unasyn®) and the tazobactam which can be found in many medicines in combination with piperacillin (such as, for example, in the medicine Tazocin®).
However, antibiotic resistance is not only caused by the production of β-lactamase by the bacteria, but can also be caused by other mechanisms.
These mechanisms include:
- Alterations in the structure of antibiotic targets;
- Creation and use of a metabolic pathway different from the one inhibited by the drug;
- Modifications of the cellular permeability towards the drug, in this way, the passage or the adhesion of the antibiotic to the bacterial cell membrane is hindered.
Unfortunately, the phenomenon of antibiotic resistance has increased considerably in recent years, mainly due to the abuse and misuse that is made of it.
Therefore, such powerful and effective drugs as beta-lactams are increasingly in danger of becoming useless due to the continuous development of resistant bacterial strains.
