Antimicrobials
Amoxicillin-Clavulanate

Amoxicillin-Clavulanate

Medium
Excellent

Dosing

General Information

Polymicrobial infections of skin & soft tissue or respiratory tract.

  • Empiric therapy of intra-abdominal infections
  • Cefazolin/cephalexin provide more narrow coverage of MSSA with favorable safety profiles
    • Consider cefazolin/cephalexin if not treating a polymicrobial infection

Prophylaxis/treatment of bite wounds.

For prolonged therapy, monitor liver enzymes and function.

  • Allergy/rash (immediate or delayed)
  • Note EBV related rash
  • Cytopenias
  • Diarrhea
  • Hepatotoxicity - usually mild; liver failure is rare

Allopurinol: Increased risk of rash

To achieve sufficient amoxicillin and high clavulanic acid exposure, the optimal regimen is to administer narrower ratio amoxicillin–clavulanic acid (4:1) in a Q8H regimen.

If medication burden or compliance are a concern, then a Q12H dosing strategy may be employed but using a broader ratio (e.g. 7:1). This broader ratio increases amoxicillin exposure (to improve efficacy) and limits clavulanic acid exposure (to reduce toxicity). 

Gram-negative organisms require higher and more sustained levels of both amoxicillin as well as the clavulanic-acid component for optimal therapy; thus for clinical syndromes in which Gram-negative pathogens are causative a narrower ratio (e.g. 4:1) with more frequent dosing (three or four rather than two times daily) is preferred (time-dependent activity). For Gram-positive pathogens, which appear to have a higher affinity for clavulanic acid and are also susceptible to lower amoxicillin concentrations, combinations with a wider ratio (e.g. 7:1) appear to be sufficient in terms of clavulanic acid exposure. In general, extreme ratios of 14:1 or 16:1 should be used with caution as there is less clinical data to support use and they may be associated with more adverse effects. 

Not all formulations are interchangeable as the ratio of amoxicillin:clavulanic acid varies. Use of an inappropriate product for a specific dosage could result in either diarrhea (which may be severe) or subtherapeutic clavulanic acid concentrations leading to decreased clinical efficacy. Some experts recommend not exceeding 10 mg clavulanate/kg/day or 125 mg clavulanate/dose.

Expressed as amoxicillin mg / clavulanate mg per 5 mL

4:1 Formulations ~500 mg/125 mg tablet (q8h dosing)
125 mg/31.25 mg per 5 mL
250 mg/62.5 mg per 5 mL
500 mg/125 mg per 5 mL

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7:1 Formulations ~875 mg/125 mg tablet (q12h dosing)
200 mg/28.5 mg per 5 mL
400 mg/57 mg per 5 mL
875 mg/125 mg per 5 mL

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Rarely used:

2:1 Formulations (children ≥ 40 kg)
250 mg/125 mg per 5 mL
Not recommended for treatment of lower respiratory tract infections or in otitis media. The total daily dose of amoxicillin using the standard dosages of this ratio is not sufficient to effectively kill the bacteria while higher dosages may result in patients receiving too much clavulanic acid.

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Rarely used:

14:1 Formulations ("high dose" regimen)
600 mg/42.9 mg per 5 mL (q12h dosing)
Generally only used for treatment of children with acute otitis media likely to have been caused by penicillin-resistant Streptococcus pneumoniae.

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16:1 Formulations ("high dose", "extended release" regimen for children and adolescents ≥ 40 kg)
1000 mg/62.5 mg per 5 mL (q12h dosing)
Generally only used for the treatment of community-acquired pneumonia that is likely to have been caused by penicillin-resistant Streptococcus pneumoniae in patients ≥ 16 years of age.

Antimicrobial class: Aminopenicillin + Beta-lactamase inhibitor

Pregnancy: Both amoxicillin and clavulanic acid cross the placenta. As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy. Consult appropriate references for more detailed information

Breastfeeding: No studies with clavulanate. See amoxicillin

Average serum half life: 1 hour

Time to peak: 1-2 hours

Distribution: ~0.36 L/kg

Urine penetration: Therapeutic

Lung penetration: Therapeutic

Biliary penetration: Therapeutic