What is the minimum inhibitory concentration (MIC) of amoxicillin?

Minimum Inhibitory Concentration (MIC) of Amoxicillin

The MIC of amoxicillin varies by organism, ranging from 0.125 mg/L for susceptible Staphylococcus aureus to 4 mg/L for Escherichia coli on standard Mueller-Hinton agar. 1

MIC Values by Organism

Gram-Positive Organisms

• Staphylococcus aureus (ATCC 29213): 0.125 mg/L on Mueller-Hinton agar, 0.5 mg/L on Iso-Sensitest agar 1
• Streptococcus pneumoniae: MICs range from 0.01 to 8 mg/L depending on penicillin resistance patterns 2, 3
  • Susceptible strains: ≤0.25 mg/L 4
  • Intermediate resistance: 2 mg/L 2, 3
  • Resistant strains: ≥4 mg/L 2, 3

Gram-Negative Organisms

• Escherichia coli (ATCC 25922): 4 mg/L on Mueller-Hinton agar, 2 mg/L on Iso-Sensitest agar 1
• Pseudomonas aeruginosa: Amoxicillin is not effective (no MIC listed in standard testing) 1

Clinical Breakpoints and Interpretation

For Streptococcus pneumoniae, the clinically validated breakpoints are: susceptible ≤1 mg/L, intermediate 2 mg/L, and resistant ≥4 mg/L. 2

• These breakpoints correlate with in vivo efficacy when amoxicillin levels exceed the MIC for 25-30% of the dosing interval 2
• Strains with MICs ≤2 mg/L showed bacterial killing of 1.4 to 4.2 log₁₀ CFU/thigh at 24 hours in animal models 2
• Strains with MICs >4 mg/L demonstrated bacterial growth despite therapy 2

Important Testing Considerations

β-Lactamase Production Effects

MIC values can be artificially low in β-lactamase-producing organisms when standard inoculum is used. 1

• Standard inoculum may result in MICs only slightly higher than susceptible strains 1
• β-lactamase production is more reliably detected by nitrocefin-based techniques in Staphylococcus, Haemophilus influenzae, and Moraxella catarrhalis 1
• Inoculum density significantly affects MIC results for Gram-negative organisms producing extracellular β-lactamases 1

MIC vs. MBC Discrepancies

The MIC more accurately predicts clinical efficacy than the MBC for amoxicillin against streptococci. 4

• Maximal bacterial killing occurs at or near the MIC concentration 4
• Higher concentrations do not increase bacterial killing beyond that achieved at the MIC 4
• MBC values can be misleadingly high (>128 mg/L) in tolerant strains, while actual bacterial reduction may still be 3 log₁₀ or greater 4

Dosing Implications Based on MIC

For severe infections with organisms at the upper susceptibility limit (MIC 8 mg/L), standard amoxicillin-clavulanate dosing achieves the 40% time above MIC target in only 65% of patients. 5

• Increasing to 6 times daily dosing improves target attainment to 95% 5
• The pharmacodynamic target of 40% time above MIC correlates with clinical efficacy 5
• Mean amoxicillin clearance in hospitalized adults is 0.17 ± 0.07 L/h/kg 5

Common Pitfalls

• Relying on MBC values alone: The MBC artificially categorizes strains as tolerant when actual bacterial killing may be adequate 4
• Ignoring β-lactamase production: Standard MIC testing may underestimate resistance in β-lactamase producers; use nitrocefin testing for confirmation 1
• Assuming standard dosing suffices: For organisms with MICs of 8 mg/L, standard dosing fails to achieve pharmacodynamic targets in 35% of patients 5
• Testing inappropriate organisms: Amoxicillin has no activity against Pseudomonas aeruginosa and should not be tested 1