In this article an infectious diseases pharmacist discusses important information for clinicians to know about antibiotic minimum inhibitory concentrations.
Authored By: Timothy P. Gauthier, Pharm.D., BCPS, BCIDP
Article posted 12 February 2024
An antibiotic’s minimum inhibitory concentrations (MIC) is the lowest drug concentration that prevents visible growth of a standard inoculum of a microorganism after ~24 hours of incubation. This is not to be confused with the minimum bactericidal concentration (MBC), which is the lowest drug concentration that prevents bacterial growth on subculture.
In this photo, the MIC and MBC are 2 mcg/mL and 8 mcg/mL, respectively. Notice how dilutions are doubling values. MICs tend to be reported as < 0.25, 0.5, 1, 2, 4, 8, 16, 23, 64, 128, > 256.
MICs can be determined through a variety of methods, all of which have limitations. One of the most common ways to calculate an MIC is on a machine such as a VITEK-2 (click the link to learn about the processes). Another method you may encounter are results from epsilometer testing (E-test), which are often done after VITEK-2 results are available. Conversely, there are now rapid tests coming to the market which will provide MIC values prior to VITEK-2 results. This is exciting and something to watch closely in years to come, because faster results help us to get the most effective and least toxic antibiotic regimen more rapidly.
Notably, disc diffusion testing (which assesses the zone of inhibition on agar plates) does not provide MIC values, but a zone of inhibition may correlate to a given MIC value in certain circumstances.
Now that we are oriented a little to what an MIC is and where it might come from, here are six things you may not know about them…
1. MIC breakpoints help us determine whether a bug-drug combination should be labeled as susceptible or resistant
Organizations such as the Clinical & Laboratory Standards Institute (CLSI) provide us with guidance on breakpoints which tell us when an MIC should cause a drug to be labeled as susceptible or resistant (or something in the middle of the two such as intermediate or dose-dependent susceptible). You can access the CLSI M100 for free here that provides these breakpoints. Just search for the organism, then look at what MIC values classify that drug for that organism.
Not all microbiology labs report MICs, but if you are seeing an E. coli listed as susceptible or resistant to a battery of drugs – then know there are MICs available somewhere that have informed those results.
2. The drug with the lowest MIC is not necessarily the drug of choice for that infection
There is an ongoing debate in the world of infectious diseases about whether to routinely report MIC values or just report the interpretation (i.e., susceptible, resistant). On one hand reporting MICs may enable providers to make nuanced decisions about antibiotic selection. On the other hand an unaware provider may mistakenly assume that the lowest MIC listed is the best drug to treat a patient with.
Just because the MIC to Drug A is 1 mcg/mL and the MIC to Drug B is 8 mcg/mL, that does not mean that Drug A is a better treatment. Picking an antibiotic depends on the how the antibiotic kills bacteria (e.g., time-dependent, concentration-dependent), how much drug reaches the site of infection, the level of antibiotic resistance that is present (i.e., MIC), and various patient-specific nuances (e.g., allergies, drug interactions). While lower is generally good when it comes to MICs, lower is not necessarily better.
If you can use cefazolin (a BB gun in terms of antibiotic spectrum of activity) or meropenem (a cannon in terms of antibiotic spectrum of activity) to treat an E. coli – why are you going to choose the cannon?
Similarly, say that the patient has cystitis with E. coli growing in a urine culture that is susceptible to ciprofloxacin at an MIC of 0.25 mcg/mL and nitrofurantoin at an MIC of 16 mcg/mL. Choosing ciprofloxacin based on it having a lower MIC would be the wrong choice, as this drug has a slew of potential toxicities that are concerning and its use should be preserved for cystitis when other alternatives are not available. Take the same patient scenario and say it is a pyelonephritis instead of a cystitis. Now picking nitrofurantoin would be a bad idea, because it does not provide adequate kidney concentrations to treat pyelonephritis, while ciprofloxacin can treat a pyelonephritis.
If you pick antibiotics by using the MIC, you may end up choosing excessively broad-spectrum antibiotics, picking more toxic antibiotics, or picking antibiotics that do not work for that infection type. There are other examples too.
3. MIC are unique to each drug-bug combination
This may seem obvious but is critical to fully appreciate. In some cases an MIC value to one drug may correlate to an MIC value to another drug. For example, an MIC of 2 mcg/mL for a Staphylococcus aureus to vancomycin has been associated with higher daptomycin MICs to that S. aureus isolate. However, more often than not, these types of comparisons are not valid. What really matters is whether the MIC interpretation based on the breakpoint for that specific drug-bug combination is an S for susceptible or an R for resistant.
4. MIC breakpoints can change over time
CLSI and other similar bodies change breakpoints periodically based on epidemiological data and other emerging information. This means that the same E. coli labeled as susceptible in 2010 may be labeled as resistant in 2025. CLSI releases updates on which breakpoints are changing and why. This information is pretty easy to access by following their news releases, but it certainly is not common knowledge. Beware that trending resistance rates over time may lead to comparing apples to oranges to bananas if the methods used to determine those rates have not been consistent (e.g., if breakpoints changed).
Interestingly, even if MIC breakpoint updates are released, it is not easy for microbiology labs to adopt them and it can take years for their adoption. A 2022 publication in Open Forum Infectious Diseases by Simner et al found that between 38% and 71% of US laboratories were using some obsolete breakpoints, with, 56% of those labs having no plans to update to current standards. They even found that 13% of laboratories were unaware of breakpoint changes or the need to update breakpoints. Thankfully there have since been some efforts to close the gap on this, but change takes time.
5. Some MICs may be available but not routinely reported
Cascade reporting and selective reporting are common practices which can help nudge prescribers towards making better antibiotic selection decisions. If cases arise where a MIC to a drug that is not commonly used is desired, calling the lab (or talking to your ID PharmD/MD) can be one way to see what additional data might be available without the need to do additional tests. It is not good to bother the good folks in the microbiology lab just for fun, but when a difficult case arises, they can be a great help.
6. Not all MIC values are reliable
Bacteria are not static, they are living. Taking their measurements in different ways can produce different results. The methods by which testing is performed can impact MIC results. Incubation for a longer or shorter period of time, incubation at varying temperatures, or changing the technology used to perform a measurement can lend to variability in a result.
In fact, and I’m quoting the ASHP vancomycin guideline here, ‘according to CLSI, acceptable MIC variability for MIC measurements is in within +/- one doubling dilution (essential agreement), such that current susceptibility testing methods are unable, with reproducibility, to distinguish MICs of 1 mg/L from 0.5 mg/L or 2 mg/L.’ The text goes on to discuss how using MicroScan vs Vitek 2 vs BD Phoenix vs E-test can produce variable results for Staphylococcus aureus.
The problem with unreliable MICs is not so much with the wild type isolates that have very low MICs which make them highly susceptible to the antibiotic. Rather the issue is more so with elevated MICs where they are at or near the breakpoint. You may recall ‘antibiotic dose optimization’ with beta-lactams has been suggested to be employed with extended infusions based on specific MIC values. Well maybe that is not a valid way to do dose optimization if the MIC you are using is not reliable. Think I am crazy? Check out this article called MIC-based dose adjustments: facts and fables.
References, Readings and Resources
- Raising the Bar: Improving Antimicrobial Resistance Detection by Clinical Laboratories by Ensuring Use of Current Breakpoints
- MIC-based dose adjustment: facts and fables
- Pharmacokinetic/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and Men
- Antimicrobial susceptibility testing to evaluate minimum inhibitory concentration values of clinically relevant antibiotic
- Clinical Impact of Revised Ciprofloxacin Breakpoint in Patients with Urinary Tract Infections by Enterobacteriaceae
- 5 Important Things To Know About Extended Spectrum Beta-Lactamases (ESBL): Insights From A Clinical Microbiologist
- Gram Negative Resistance Mechanisms: A Leading Pharmacist’s Clinical Perspectives On AmpC, ESBL and KPC
- Five Moments For Antimicrobial Stewardship Using Microbiology Results
Disclaimer
The views and opinions in this article represent those of the author and may not reflect the policy or position of any previous, current, or potential future employer.
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