Amoxicillin/clavulanate

Antibiotic Class:

Beta-lactam/beta-lactamase inhibitor

Antimicrobial Spectrum:

Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli

Mechanism of Action:

The beta-lactamase inhibitors are recognized as substrates for the beta-lactamases produced by bacteria. This allows the actual beta-lactams to attack the bacterial cell wall by binding to penicillin binding proteins

Pharmacodynamics:

Time dependent killer (Time > MIC)

Pharmacokinetics:

(of the clavulanic acid)

Dose 200mg: Cmax: 8.5-14.3 mcg/L; Protein binding: 20%; Volume of distribution: 0.16-0.25L/kg; Table 5

Adverse Effects:

No new adverse effects are seen as a result of adding beta-lactamase inhibitors to beta-lactam antibiotics. The adverse reactions would remain the same for the parent compound

Dosage:

PO: Complete listing on Table 6

Dosing in adults:

Mild/Moderate: 250mg q8h to 500mg q8h

Severe: 875mg-2000mg q12h

Dosing in pediatrics:

Mild/Moderate: 20-25mg/kg/day divided q8h

Severe: 40-45mg/kg/day divided q8h

Table 8

Disease state based dosing:

Renal failure:  CrCl > 30mL/min: 500mg q8-12h or 875mg q12h

                       CrCl 10-30mL: 250-500mg q12h

                       CrCl < 10mL/min: 250-500mg q24h

Hepatic failure:  No dosing changes recommended at this time.

Contraindications/Warnings/Precautions:

Precautions:  hypersensitivity to penicillins, history of gastrointestinal disease, particularly colitis, renal impairment

Drug Interactions:

Acenocoumarin increased risk of bleeding; Allopurinol higher probablility of amoxicillin rash; Contraceptives - decreased contraceptive effectiveness; Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine; Methotrexate methotrexate toxicity; Probenecid - increased amoxicillin levels; Warfarin increased risk of bleeding

Pregnancy:

Category B: No evidence of risk in humans but studies inadequate.

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, serum levels, signs and symptoms of infection, white blood cell count

Toxic: Urinalysis, BUN, SCr, AST and ALT, skin rash, Neutropenia and leukopenia,

Brand names/Manufacturer: 

Augmentin/GlaxoSmithKline