AMR: ORGANISM SUSCEPTIBILITIES TO ANTIBIOTICS; MISCONCEPTIONS ASSOCIATED WITH MICS

by Dr. Ethan Levy

MIC refers to the Minimum Inhibitory Concentration of a given antibiotic (AB) required to inhibit the growth of a specific microorganism. Typically these will either be reference organisms or biological agents isolated from clinical sources. There are two key conceptual words to consider: minimum and inhibition. When subjected to the inhibitory range of a biologically active compound (AB) the microbe is immediately put under a situation referred to selective pressure where it maintains its viability but it ceases to grow (elongate and divide) It is during this period when an organism, using intracellular reserves, may shuffle it’s genetic mechanisms (e.g. plasmids) to produce compounds e.g. enzymes, to breakdown the encountered antimicrobial and overcome its growth suppressive action.

Coincidental with inhibition, sub populations of resistant organisms begin to emerge. This is why MIC breakpoint values, typically scored at 24 hours (Figure 1), will change over time (Figures 2 and 3). How can we realize a drug’s potential to induce adaptation? If we consider the MBC value or the Minimum Bacteriocidal Concentration (where organism viability is completely lost) and compare it to the MIC value a ratio can be obtained. The further the spread (in dilution) between the MIC and MBC values, the greater the potential for adaptation and resistance to the antibiotic agent, often with the consequential formation of a Super-Bug. MIC breakpoint values are not very accurate and will change with time. Consider that a clear tube or well could contain up to Nx10^6 microbes/ml. with numerous sub populations, each at a different stage in life cycle (Figure 4). The MBC value on the other hand, if determined properly (with proper neutralization of any AB carryover), while not absolute, is a far more definitive measurement of biological activity or potency.

Another typical misconception is that an MIC value represents the strength of activity or potency of a given drug (AB). This is not true. It is representative of a given organisms response to that drug. In other words it’s a value associated with the specific microbial strain in test .

Improper interpretations associated with MICs especially when taken that one reference strain is representative of all species specific strains will lead to eventual therapeutic failures and AMR.

Based on available PK and PD information, the CLSI has recently introduced the concept of Susceptible Dose Dependent (SDD) as a new interpretive category for certain antibiotic organism combinations. SDD information will enable clinicians to use increased dosages of a given antibiotic as a safe option to ensure therapeutic success and help prevent resistance.

Figure 1: MIC breakpoint value for AB(1) and AB(3) showing values 4 and 8 mcg/ml respectively at 24 hours of incubation. Microbial growth is indicated by yellow wells.

Figure 2: Changed MIC breakpoint values showing 6 and 12 mcg/ml for AB(1) and AB(3) respectively at 48 hours of incubation

Figure 3: At 72 hours of incubation, MIC values for AB(1) and AB(3) have further changed to 8 and 16 mcg/ml respectively.

Figure 4: Depicts the presence of viable subpopulations of organisms in their various phases of growth which will eventually develop into visible turbidity.

References:

CLSI Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. M100. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; 11th Approved Standard M07 (2021) Clinical and Laboratory Standards Institute. Wayne, Pa.

AMR Insights Ambassador Network

Dr. Ethan Levy is a member of the Global AMR Insights Ambassador Network. The AMR Insights Ambassador Network consists of an integrated global community of professionals which identify, share and discuss action plans to combat AMR. The Network strives to inspire, connect and empower the ambassadors to implement strategies to curtail AMR. For more information about the Network: https://www.amr-insights.eu/about-us/ambassadors.