Generality
Clavulanic acid is a compound having a beta-lactam (or β-lactam) type chemical structure. In particular, clavulanic acid is a β-lactamase inhibitor that is widely used in medicinal preparations in association with antibiotic drugs, such as penicillins.
Uses of Clavulanic Acid
Although clavulanic acid has a weak antibacterial activity, its use in medicinal preparations with antibiotic action is not carried out due to its direct action against microorganisms, but because of its ability to inhibit particular enzymes produced by different strains bacterial: β-lactamases (or beta-lactamases).
Β-lactamases are particular enzymes (more precisely, of serine proteases) produced by certain bacterial strains, to which they confer resistance to antibiotics with a beta-lactam chemical structure (such as, for example, penicillins). In fact, the task of these enzymes is precisely to break the beta-lactam ring present in the structure of the aforementioned antibiotic drugs, irreversibly compromising their activity and allowing the bacteria to survive.
Clavulanic acid is used above all in association with amoxicillin (a semisynthetic broad-spectrum penicillin). There are several medicinal preparations based on amoxicillin and clavulanic acid on the market; among the most known we remember the Augmentin® and the Clavulin®.
Action mechanism
As mentioned, clavulanic acid is an irreversible inhibitor of the aforementioned beta-lactamases. Having a beta-lactam chemical structure, clavulanic acid is able to bind to these enzymes in a preferential way compared to penicillins.
More in detail, clavulanic acid - by binding to beta-lactamases instead of penicillins - causes the irreversible acylation of serine hydroxyl present in the active site of the same enzyme, inhibiting it.
In truth, some types of beta-lactamases are able to hydrolyse clavulanic acid; however, following such hydrolysis, successive chemical reactions take place which in any case lead irremediably to the inhibition of the enzyme, thus allowing the desired effect to be obtained in any case.
Precisely because of this mechanism of action, clavulanic acid is included in the group of what are called " β-lactamase suicide inhibitors ".
Advantages
Thanks to the use of clavulanic acid in association with penicillins - and, in particular, to amoxicillin - it has been possible to extend the activity of these antibiotics also with regard to beta-lactamase-producing bacteria (which otherwise would be resistant to the action antibacterial of the aforementioned drugs).
Therefore, it can be stated that the association of clavulanic acid with amoxicillin has allowed us to significantly and significantly expand the spectrum of action. In particular, this association is particularly effective in the event of:
- Infections of the airways, such as sinusitis, exacerbations of chronic bronchitis and otitis caused by bacterial strains of Haemophilus influenzae and Moraxella catarrhalis that produce beta-lactamases;
- Urinary tract infections sustained by Gram-negative bacteria and Staphylococcus saprophyticus ;
- Mild infections sustained by aerobic flora and anaerobia.
Side effects
Since clavulanic acid is never used alone, it is difficult to determine what side effects it may have caused.
However, it has been observed that - with respect to the administration of the single amoxicillin - the administration of the latter in association with clavulanic acid causes with greater incidence gastrointestinal side effects, particularly diarrhea. However, this effect can be significantly reduced by administering the medicine on a full stomach.
In addition to this, it seems that the association of clavulanic acid with amoxicillin also causes an increase in the incidence of more serious adverse effects, such as acute hepatitis, cholestatic jaundice, Stevens-Johnson syndrome and purpura.
Contraindications
Usually, the use of clavulanic acid in combination with penicillins is not recommended for the treatment of acute bronchopulmonary infections, since it has a reduced ability to penetrate bronchial secretions.
However, the choice of administering the single amoxicillin or the association of the latter with clavulanic acid is entirely up to the doctor who will evaluate case by case which therapeutic strategy is best suited to the individual patient.
