Generic Name

Augmentin

Mechanism

• Amoxicillin: Binds to penicillin‑binding proteins (PBPs) on the bacterial cell wall, inhibiting peptidoglycan cross‑linking → cell lysis.
• Clavulanic acid: Irreversibly inhibits a wide variety of β‑lactamases, safeguarding amoxicillin from enzymatic degradation.
• The combination allows effective treatment of infections caused by β‑lactamase–producing Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Pharmacokinetics

• Absorption: Oral; bioavailability ≈ 75 % for the amoxicillin/clavulanic acid ratio 4:1 (≈600 mg/150 mg).
• Peak plasma concentration (Cmax): ~4–5 µg/mL for amoxicillin, ~1 µg/mL for clavulanic acid, within 1–2 h post‑dose.
• Distribution: Widely distributed; penetrates respiratory tract, sinuses, otic space, and mild penetration into CSF (especially with meningitis).
• Metabolism: Minimal hepatic metabolism; clavulanic acid is partly glucuronidated.
• Elimination: Renal excretion unchanged; half‑life 1–1.5 h (amoxicillin) and 0.7–1 h (clavulanic acid).
• Dose adjustments: Primarily needed in renal impairment (dose reduction or altered interval).

Indications

*Regimens may vary by local guidelines and resistance patterns.*

Contraindications

• Contraindications:
• Hypersensitivity to amoxicillin, clavulanic acid, penicillins, or cephalosporins.
• History of severe allergic rash (Stevens–Johnson syndrome, toxic epidermal necrolysis).
• Warnings:
• Clavulanate‑related hepatotoxicity: Monitor LFTs in patients with liver disease.
• Clostridioides difficile colitis: Counsel patients on signs of severe diarrhea; consider alternative agents if high risk.
• Pregnancy: Category B; generally safe but avoid during lactation (drug secreted in breast milk).
• Renal impairment: Use caution; adjust dose in CrCl < 30 mL/min.
• Prophylactic use in dentistry: Consider alternative agents for patients with β‑lactam allergy.

Dosing

• Duration: 7–14 days for most infections; longer courses for severe or complicated infections (20–21 days in intra‑abdominal or septic arthritis).

Adverse Effects

• Common (> 10 %):
• Diarrhea, nausea, vomiting, epigastric discomfort.
• Skin rash (maculopapular).
• Mild hepatotoxicity (elevated transaminases).
• **Serious ( 10 % of body surface area or systemic symptoms.*

Monitoring

• Baseline: CBC, LFTs, renal function (CrCl).
• During therapy:
• CBC if eosinophilia or neutropenia is suspected.
• LFTs in patients with pre‑existing liver disease or prolonged courses.
• Renal adjustment: Re‑calculate dose if CrCl falls below 30 mL/min.
• Adverse event surveillance:
• Monitor for diarrhea; if severe, evaluate for C. difficile.
• Watch for rash or anaphylaxis; advise early contact.

Clinical Pearls

• β‑Lactamase protection: Clavulanic acid “covers” β‑lactamases that would otherwise inactivate amoxicillin—great for β‑lactam‑resistant H. influenzae and S. pneumoniae.
• Microdosing for dental prophylaxis: 600 mg/150 mg twice daily for 3–5 days is effective and reduces the systemic load compared with broader agents.
• Food interaction: Taking Augmentin with food can mask GI upset but may delay absorption by ~30 min—acceptable for most indications.
• IV route: Requires 5–10 % saline solution due to potential precipitation at high concentrations; add IV vancomycin or aztreonam to avoid incompatibility.
• Pregnancy & lactation: Safe during pregnancy but contraindicated in nursing infants ≤ 2 months due to potential for ototoxicity and hearing impairment.
• Avoid in patients with renal insufficiency: Clavulanic acid is renally excreted; accumulation increases risk of neurotoxicity in severe renal failure.

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• References
• U.S. FDA Label for Augmentin (Augmentine) (2023).
• European Medicines Agency: Augmentin prescribing information (2024).
• Baddour LM, et al. *Antibiotic stewardship and optimal dosing of β‑lactams.* Clin Infect Dis. 2022.

For further reading, consult the latest *Clinical Infectious Diseases* guidelines on β‑lactam/β‑lactamase inhibitor use.