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Emergency

MICs

MICs

Minimum inhibitory concentrations (MICs) are considered the `gold standard’ for determining the
susceptibility of bacteria to antimicrobials and tells you what minimum antimicrobial concentration
you need to achieve in order to inhibit the growth of a micro-organism (low values = sensitive; high
values=resistant). Concentration dependent antimicrobials indicate that therapeutic success will be
achieved when peak concentration of 8-10 x MIC is attained. Time-dependent antimicrobials aim to
exceed the MIC for as long as possible (at least 50% of the time).

MIC calculation. All vials are inoculated. Turbidity (bacterial growth) is present at
0.1–0.8 microg/mL, but not at 1.6-51.2 microg/mL. MIC = 1.6 microg/mL. This is the
minimum target concentration for time dependent antimicrobials to be maintained
for at least 50% of the time. For concentration dependent antimicrobials the target
is 8-10 x MIC = 12.8-16 microg/mL.
Time dependent antimicrobials Concentration dependent antimicrobials
Aim: exceed MIC for >50% of dosing interval Aim: achieve peak concentration of 8-10 x MIC
Beta lactams – penicillins and cephalosporins Aminoglycosides (gentamicin, amikacin)
Tetracyclines Fluoroquinolones (enrofloxacin)
Sulphonamides Metronidazole
Macrolides (azithromycin, clarithromycin)

From combining the knowledge of systemic drug concentrations at standard doses, MIC “breakpoint
concentrations” are determined – above which resistance (R) is predicted (as this represents
unrealistic concentrations) and below which sensitivity (S) is predicted (as such concentrations can be
readily achieved). Depending on the drug and MIC, it is possible that modification of the dose might
achieve therapeutic success when the MIC value is only just above the S/R breakpoint; additionally
infection at sites where drug tends to accumulate (e.g. penicillins and aminoglycosides in urine) may
find clinical success when resistance is predicted.

Compared with simple binary results stating resistant/sensitive, MIC values give a more quantitative
impression of how sensitive or how resistant an organism is (lower MIC is better – i.e. more sensitive).
From the example above, if we know we can achieve tissue concentrations of 4 microg/mL with a
particular antibiotic then this will be reported as sensitive (S). In contrast, if we know we can only
achieve 0.25 microg/mL with a particular drug then this will be reported as resistant (R). However, if
we know we can usually achieve around 2-3 microg/mL (reported as R) then we could use a higher
than normal dose and still possibly achieve success (as long as higher doses aren’t toxic).
Low MIC values indicate a greater likelihood of achieving the relevant target concentrations with
systemic treatment whereas high values indicate that systemic therapy is likely to fail, although
adequate concentrations might still be reached with local treatments (e.g. intraocular, intrauterine)
or circumstances where especially high concentrations can be achieved (e.g. intravenous regional
perfusion). To make best use of MIC values, an idea of readily identifiable systemic drug
concentrations is required.
Example 1.

  • 10 day old septicaemic foal
  • Blood culture isolates Actinobacillus equuili
  • Gentamicin MIC calculated to be 2 microg/mL
  • a “concentration dependent” an bio c needs to reach 8-10 x MIC (16-20 mg/mL)
  • Gentamicin 6.6 mg/kg iv (typically achieves plasma concentrations >20 microg/mL)
    Example 2
  • Adult horse with peritonitis
  • Peritoneal fluid isolates Streptococcus zooepidemicus
  • Penicillin MIC calculated to be <0.06 microg/mL
  • a “ time-dependent” antibiotic needs to exceed MIC (0.06 mg/mL) for as long as possible
  • Give procaine penicillin 22,000 IU/kg im q 12 hrs (typically achieves peritoneal
    concentrations 0.5 microg/mL)
    Example 3
  • Corneal ulcer
  • Swab isolates Moraxella sp.
  • Gentamicin MIC = 16 microg/mL (resistant)
  • you must achieve 8-10 x MIC (130-160 microg/mL)
  • impossible to reach with systemic treatment
  • However, 3 drops 0.5% gentamicin drops à >350 microg/mL in tear film
  • topical gentamicin should be effective despite lab prediction of resistance
    Example 4
  • Mare with bacterial cystitis
  • E.coli isolated
  • Gentamicin MIC = 16 microg/mL (‘resistant’)
  • Need 8-10 x MIC (130-160 microg/mL)
  • 6.6 mg/kg gentamicin à 20-30 microg/mL in plasma
  • 2 mg/kg gentamicin à 425 microg/mL in urine
  • Low dose systemic gentamicin should be effective despite lab prediction of resistance