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Saturday, July 26, 2025

Co-amoxiclav


Co-amoxiclav is a widely used broad-spectrum antibacterial combination drug consisting of:

  • Amoxicillin: A beta-lactam antibiotic (penicillin group)

  • Clavulanic acid (clavulanate potassium): A beta-lactamase inhibitor

Clavulanic acid protects amoxicillin from degradation by bacterial enzymes called beta-lactamases, which would otherwise render amoxicillin ineffective against resistant strains. This combination extends amoxicillin's spectrum of activity, especially against beta-lactamase-producing bacteria, making co-amoxiclav effective in many community-acquired and hospital-acquired infections.

Brand Names

  • Augmentin® (original brand by GlaxoSmithKline)

  • Curam®

  • Clavulin®

  • Amoclan®

  • Synulox® (veterinary use)

  • Many generics available worldwide

Available Formulations

Oral

  • Tablets (e.g., 375 mg, 625 mg, 1 g)

    • 250/125 mg: amoxicillin 250 mg + clavulanic acid 125 mg

    • 500/125 mg

    • 875/125 mg

    • 1000/62.5 mg (high-dose amoxicillin)

  • Suspensions (e.g., 125/31.25 mg per 5 mL; 400/57 mg per 5 mL) – pediatric use

Parenteral (IV)

  • Vials for reconstitution

    • Common dose: 500 mg/100 mg, 1 g/200 mg, 2 g/200 mg

  • Hospital settings only

Mechanism of Action

Amoxicillin:

  • Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs)

  • Effective against many Gram-positive and some Gram-negative organisms

  • Bactericidal

Clavulanic acid:

  • A suicide inhibitor of beta-lactamases produced by resistant bacteria

  • Irreversibly binds to enzymes that would destroy amoxicillin

  • Has little intrinsic antibacterial activity but greatly extends amoxicillin’s spectrum

Spectrum of Activity

Effective against:

  • Streptococcus species (incl. S. pneumoniae)

  • Staphylococcus aureus (non-MRSA)

  • Haemophilus influenzae

  • Moraxella catarrhalis

  • Escherichia coli

  • Klebsiella spp.

  • Proteus spp.

  • Neisseria gonorrhoeae

  • Bacteroides spp.

  • Pasteurella multocida

Not effective against:

  • MRSA (methicillin-resistant Staph aureus)

  • Pseudomonas aeruginosa

  • Atypicals (e.g., Mycoplasma, Chlamydia)

Therapeutic Uses

Co-amoxiclav is indicated for the treatment of bacterial infections caused by susceptible organisms, especially where beta-lactamase resistance is likely:

  • Respiratory tract infections

    • Community-acquired pneumonia

    • Acute bacterial sinusitis

    • Otitis media

    • Chronic bronchitis exacerbations

  • Urinary tract infections (UTIs)

  • Skin and soft tissue infections

    • Cellulitis

    • Animal bites

    • Diabetic foot infections

  • Dental infections

    • Dental abscess

    • Periodontal infections

  • Bone and joint infections

    • Osteomyelitis

  • Intra-abdominal infections

    • Diverticulitis

    • Peritonitis

  • Gynecological infections

  • Sepsis of unknown origin

Also used in surgical prophylaxis in specific procedures (e.g., gastrointestinal, gynecologic, head/neck surgeries).

Dosage and Administration

Adults and Children ≥40 kg:

  • Mild/moderate infections:
    500/125 mg every 8 hours

  • Severe infections:
    875/125 mg or 1000/62.5 mg every 12 hours

  • Duration: Usually 5–7 days for mild infections, up to 14 days for severe infections

Children <40 kg:

  • 20–40 mg/kg/day (based on amoxicillin) in divided doses for mild infections

  • 40–90 mg/kg/day in divided doses for severe infections (e.g., otitis media, sinusitis)

  • Use suspension; dose varies with formulation concentration

IV Use (Hospital):

  • 1.2 g IV every 8 hours for most infections

  • Up to 2.2 g IV every 8 hours for severe infections

  • Adjust for renal impairment

Renal Impairment:

  • Reduce frequency and dose depending on creatinine clearance

  • Clavulanic acid accumulation is more pronounced—requires caution

Contraindications

  • Known hypersensitivity to penicillins or beta-lactam antibiotics

  • History of cholestatic jaundice or hepatic dysfunction associated with previous co-amoxiclav use

  • Severe hepatic impairment

Precautions and Warnings

  • Use cautiously in patients with:

    • Hepatic dysfunction

    • Renal impairment

    • History of antibiotic-associated colitis

  • Monitor liver function in long-term or high-dose use

  • Watch for allergic reactions, especially in patients with asthma or other allergies

  • Prolonged use may lead to fungal or resistant bacterial superinfection

Side Effects

Common

  • Diarrhea

  • Nausea and vomiting

  • Abdominal pain

  • Rash

  • Candidiasis (oral/vaginal)

  • Skin reactions (e.g., urticaria)

Uncommon to Rare

  • Liver enzyme elevation

  • Cholestatic hepatitis or jaundice

  • Allergic reactions (anaphylaxis, angioedema)

  • Clostridioides difficile-associated diarrhea

  • Seizures (in renal impairment or high doses)

  • Interstitial nephritis

Drug Interactions

  • Allopurinol: Increases risk of rash

  • Warfarin: May increase INR, requiring closer monitoring

  • Methotrexate: Amoxicillin can reduce renal excretion → toxicity

  • Oral contraceptives: May reduce efficacy due to gastrointestinal upset

  • Probenecid: Delays renal excretion of amoxicillin

Pregnancy and Lactation

Pregnancy

  • Considered safe in pregnancy (Category B – no evidence of harm)

  • Used routinely for UTIs, respiratory infections

Lactation

  • Excreted in breast milk in small amounts

  • Generally considered safe, but may cause diarrhea or candidiasis in infants

Microbiological Considerations

  • Co-amoxiclav is often used empirically, especially for community-acquired infections

  • Resistance increasing due to:

    • Overuse

    • Extended-spectrum beta-lactamase (ESBL)-producing organisms (not susceptible)

  • Best used when beta-lactamase production is suspected or proven

Storage

  • Tablets: Store at room temperature (15–25°C)

  • Oral suspension (reconstituted): Refrigerate; discard after 7–10 days

  • IV vials: Reconstitute immediately before use; use within recommended time frame

Patient Counseling Points

  • Take at the start of a meal to improve absorption and reduce GI upset

  • Complete the full course, even if symptoms improve

  • Diarrhea is common; if severe or watery, seek medical attention (may be C. difficile)

  • Report rash, itching, or breathing difficulties immediately

  • Store liquid suspension in refrigerator; shake well before each use

  • Avoid alcohol if GI upset occurs

Clinical Guidelines and Recommendations

  • Included in WHO Essential Medicines List

  • Recommended by NICE, IDSA, and SIGN for various infections

  • Widely used in:

    • NHS prescribing formularies

    • Hospital antibiotic protocols

    • Primary care guidelines for dental and ENT infections



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