clavulanate

Clavulanate refers to clavulanic acid, a beta-lactamase inhibitor produced by Streptomyces clavuligerus. In clinical use it is typically supplied as a salt form (such as potassium clavulanate) and combined with a beta-lactam antibiotic, most commonly amoxicillin, to counteract bacterial enzymes that inactivate penicillins. Clavulanate itself has limited intrinsic antimicrobial activity.

Mechanism of action: Clavulanate inhibits many serine beta-lactamases, particularly class A enzymes, by acting as a suicide inhibitor that becomes covalently bound to the enzyme. This protects the accompanying beta-lactam antibiotic from hydrolysis, thereby extending its spectrum of activity against beta-lactamase–producing organisms. The inhibitor is often more effective against certain enzymes than others and provides variable protection depending on the bacterial strain and the antibiotic partner.

Clinical use: Clavulanate is most commonly used in fixed combinations with amoxicillin to treat infections where beta-lactamase production would limit penicillin efficacy. These combinations broaden activity against many respiratory pathogens (for example, Haemophilus influenzae and Moraxella catarrhalis), certain enteric bacteria, and various skin and soft tissue and intra-abdominal pathogens. Indications typically include respiratory tract infections, sinusitis, otitis media, skin and soft tissue infections, and mild-to-moderate intra-abdominal infections.

Pharmacology and safety: After oral administration, clavulanate is absorbed alongside the partner antibiotic; it is primarily eliminated via the kidneys and has a short elimination half-life. Common adverse effects include gastrointestinal upset, diarrhea, and rash; serious hepatotoxicity is rare but has been reported. Use requires caution in penicillin-allergic individuals, and monitoring is advised in patients with hepatic or renal impairment.

Resistance and history: The combination remains valuable in addressing beta-lactamase–mediated resistance, though organisms with non–beta-lactamase mechanisms may still resist therapy. Clavulanic acid was identified in the 1970s and widely adopted in amoxicillin-clavulanate formulations.