Co-amoxiclav: A broad-spectrum antibiotic with a beta-lactamase inhibitor

What it is

Co-amoxiclav is a combination of amoxicillin (a beta-lactam antibiotic) and clavulanic acid (a beta-lactamase inhibitor). The combination broadens the spectrum to cover bacteria that produce beta-lactamase enzymes, which make plain amoxicillin useless.

It is one of the most prescribed antibiotics in primary care for mild to moderate community infections of the airways, urinary tract and skin. It comes in several strengths and formulations.

Mechanism of action

It works through:

Amoxicillin: inhibition of bacterial cell wall synthesis (bactericidal)
Clavulanic acid: it blocks the bacterial beta-lactamases that would destroy the amoxicillin
Together: activity is restored against beta-lactamase-producing bacteria

At the counter

When to recommend it

Respiratory infections (otitis, sinusitis, acute bronchitis)
Some urinary infections, according to local guidelines or the culture result
Skin and soft tissue infections (impetigo, mild cellulitis)
Dental abscesses that are spreading

When not to

Allergy to beta-lactams (penicillin, cephalosporins)
Infectious mononucleosis (risk of rash)
History of jaundice or liver damage with co-amoxiclav
Suspected serious infection needing hospital care

What to say at the counter. When supplying it: take it at the start of a meal (it improves tolerance), for as long as the doctor has said, and warn that mild diarrhoea is common but severe diarrhoea, diarrhoea with blood or with fever means seeing a doctor.

Warnings

Important Cross-allergy: patients allergic to penicillin can also be allergic to this. Check the history.
Important C. difficile-associated (pseudomembranous) diarrhoea: rare but serious. Warn the patient about severe diarrhoea with blood.
Caution Mild to moderate diarrhoea: very common, because the gut flora is wiped out. Recommend a probiotic.
Caution Kidney failure: the dose needs adjusting when GFR is below 30 mL/min.

Pharmacokinetics

Absorption: Rapid absorption after oral administration. Bioavailability around 90%. Onset of action at 1–2 hours. Clavulanic acid is absorbed just as quickly.
Distribution: Wide distribution in body tissues. Good penetration into the lungs, ears and urinary tract. Moderate plasma protein binding (20%). It crosses the placenta.
Metabolism: Amoxicillin is barely metabolised; clavulanic acid is partly metabolised in the liver.
Elimination: Mainly renal (amoxicillin largely unchanged). Half-life of 1–1.5 hours.

Co-amoxiclav vs amoxicillin

Aspect	Co-amoxiclav	Amoxicillin
Antibacterial spectrum	Broad (covers beta-lactamase)	Narrower
Activity against S. aureus	Good (if not MRSA)	Poor
Cost	Higher	Lower
Gastrointestinal tolerance	Slightly worse (clavulanic acid irritates)	Better
First-line indication	Infections at risk of beta-lactamase	Simple susceptible infections

Co-amoxiclav if beta-lactamase production or resistance is suspected. Amoxicillin alone for a simple susceptible infection (and it is cheaper).

Self-assessment

Three questions. When you check your answers you will see the explanation for each one.

What does clavulanic acid do in this combination? It boosts amoxicillin's antibacterial activity It reduces the diarrhoea caused by amoxicillin It blocks the beta-lactamase enzymes that destroy amoxicillin
A patient allergic to penicillin asks whether they can take co-amoxiclav. Your answer? Yes, but only if the allergy was mild Yes, because clavulanic acid is not a penicillin No, because amoxicillin is a penicillin and there is a risk of cross-reaction. They should speak to their doctor
Which very common side effect of co-amoxiclav should you warn the patient about? Raised blood pressure Diarrhoea, usually mild to moderate, from the disruption of the gut flora Severe liver toxicity

Training content. It does not replace the summary of product characteristics or clinical judgement.

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