MIC KEY

M-O-U-S-E? No.

 

The minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit growth of a certain microbe.  In the United States, the Clinical and Laboratory Standards Institute (CLSI) provides standardization of MIC determinations and publish guidelines regularly (the European organization is EUCAST).  Each antimicrobial listed in a culture report will be assigned one of three breakpoints determined by CLSI: “susceptible,” “intermediate,” or “resistant.” 

Many factors, including laboratory and clinical information, determine the interpretation of reported MIC breakpoints.  The term “breakpoint” can be thought of three different, yet interrelated, ways. A microbiologic breakpoint is determined by a multitude of in vitro tests evaluating the physical interaction of the drug with the microbe.  A clinical breakpoint factors in whether there is a good chance of infection resolution, mainly based off of clinical studies.  Similar to a clinical breakpoint, pharmacokinetic/pharmcodynamic breakpoints factor for such things as location of infection and ability to obtain proper drug levels in that area of the body.

Let us use the drug daptomycin for a VRE pneumonia as an example.  The drug may have excellent bacteriocidal activity against the specific cultured organism in vitro, but when factoring in clinical and PK/PD data, we know lung surfactant inactivates daptomycin.  We would not be able to successfully treat the infection with this antimicrobial agent.  The MIC report might state “susceptible” in vitro, but clinically it may as well be regarded as resistant. 

Sooo…can’t I just pick the drug with the lowest number next to it that says “susceptible?”

Apples and oranges, my friend.  It is not useful to compare the MIC concentration value of one drug to another.  The MIC expressed in “mg/L” is unique to each drug based off of PK/PD data done with fancy modeling and simulations.  The determination of what concentrations to use when setting up dilutions to test MICs incorporate things like protein binding, tissue distribution, and even the type of bug that was cultured.  Let’s look at an example:

Source: Urine

E. coli >100,000/mL

Status: Final

Results:

Ampicillin

>/= 16

Resistant

Cefazolin

4

Susceptible

Ciprofloxacin

</= 0.5

Susceptible

Gentamicin

</= 2

Susceptible

Nitrofurantoin

</= 32

Susceptible

Piperacillin/Tazobactam

</= 8

Susceptible

 

Just strictly looking at numbers, it appears ciprofloxacin would be better than the rest since its MIC is </= 0.5 mg/L.  Nitrofurantoin, even though the report says susceptible, has a larger MIC concentration of </= 32 mg/L.  Both would eradicate this microbe with similar efficacy.  Cefazolin has a value of 4 mg/L.  Notice that it does not have the “</=” designation.  This means the MIC for cefazolin is right at the breakpoint of susceptible and intermediate – an MIC of 8 mg/L may read as intermediate.  The number would still be less than 32 such as for nitrofurantoin but would possibly have less chance of clearing the infection.  Also note that resistance is reported for an MIC of 16 for ampicillin.  Even though it is less than 32, the likelihood of ampicillin clearing the infection would be low.

The key to correctly interpreting this data is to also incorporate antimicrobial stewardship.  If this is an otherwise healthy young female with an uncomplicated cystitis, nitrofurantoin should be the drug of choice.  Although other antibiotics are listed as “susceptible,” it’s like using a shotgun when a Nerf gun would do the job.  Nitrofurantoin is only used for this indication and should be considered first.  Ciprofloxacin would cure the infection and isn’t wrong to use in this situation, but we should preserve our use of it for silly things like anthrax and pseudomonas.

 

Bottom Line:

  • Interpreting culture results appropriately requires an appreciation for the microbe species and location of infection
  • Comparing MIC concentrations between different drugs is like comparing apples and oranges
  • Utilizing an antibiotic with the “</=” designation may be your best bet
  • Exercise antimicrobial stewardship and choose the lowest-spectrum antimicrobial that will get the job done
  • Consult your friendly pharmacist for assistance