clavulanic

Clavulanic acid, also known as clavulanate, is a beta-lactamase inhibitor produced by the soil bacterium Streptomyces clavuligerus. It is not a stand-alone antibiotic but is used to broaden the activity of certain beta-lactam antibiotics by protecting them from bacterial enzymes that inactivate many penicillins.

Mechanism of action

Clavulanic acid acts as a mechanism-based (suicide) inhibitor of serine beta-lactamases. It binds to the active site of these enzymes and forms a covalent complex, thereby inactivating the enzyme. This preserves the integrity of co-administered beta-lactam antibiotics, allowing them to reach their targets in resistant bacteria. Its inhibitory activity is selective and does not extend to all beta-lactamases; it is less effective against AmpC-type enzymes and many carbapenemases.

Clinical use

In clinical practice, clavulanic acid is combined with penicillins to create expanded-spectrum formulations, the most common being amoxicillin-clavulanate. Other combinations with clavulanate include ticarcillin-clavulanate and piperacillin-clavulanate. These products are used to treat mixed infections and infections caused by beta-lactamase–producing organisms, such as certain respiratory, sinus, skin, and intra-abdominal infections. Clavulanic acid has minimal activity as an antibiotic on its own.

Pharmacokinetics and safety

Clavulanic acid is administered orally or by injection in fixed-dose combinations. It is absorbed from the gastrointestinal tract and is primarily cleared by the kidneys, with dose adjustments needed in renal impairment. Common adverse effects include gastrointestinal symptoms (such as diarrhea and nausea) and rash; hypersensitivity reactions can occur. Rare cases of liver enzyme elevations or hepatic injury have been reported, and interactions with other drugs (for example, valproate) can occur.

History and structure

Clavulanic acid was isolated from Streptomyces clavuligerus in the 1970s. It is part of a broader class of beta-lactamase inhibitors that includes sulbactam and tazobactam, often used in combination with beta-lactam antibiotics.