MIC

**Definition:** MIC is the lowest concentration of an antimicrobial agent that inhibits visible growth of a microorganism after ~16-24 h of incubation. It is a measure of bacteriostatic activity.

**How it is measured:** - Broth dilution (macro or microdilution): serial 2-fold dilutions of drug are inoculated with a standardized bacterial suspension. The MIC is the first tube or well with no turbidity. - Agar dilution. - Gradient diffusion (E-test): a strip with a drug gradient is placed on an agar plate. The MIC is read where the ellipse of inhibition meets the strip. - Automated systems (e.g., VITEK, MicroScan). - Kirby-Bauer disk diffusion gives zone diameters, not MICs. Zone sizes are correlated with MIC breakpoints.

**Interpretation:** - The MIC is compared with clinical breakpoints (CLSI or EUCAST) to report an isolate as Susceptible (S), Intermediate/Susceptible-dose dependent (I/SDD), or Resistant (R). - Breakpoints reflect achievable drug levels at the infection site, PK/PD, and clinical outcome data. - A lower MIC does not mean a better drug. A drug with an MIC of 0.5 may not be better than another with an MIC of 4 if their breakpoints and tissue levels differ. - MIC90 or MIC50 is the concentration inhibiting 90% or 50% of isolates in a population. These are used in surveillance.

**Related terms (high-yield):** - **MBC (Minimum Bactericidal Concentration):** the lowest concentration that kills ≥99.9% of the initial inoculum. It is determined by subculturing from clear MIC tubes onto drug-free media. - **Bactericidal vs. bacteriostatic:** an MBC/MIC ratio ≤4 suggests bactericidal activity. A ratio >4 suggests bacteriostatic activity or tolerance. - **Bactericidal drugs (mnemonic):** β-lactams, aminoglycosides, fluoroquinolones, vancomycin, daptomycin, metronidazole, isoniazid, rifampin, and pyrazinamide. - **Bacteriostatic drugs (mnemonic "We're ECSTaTiC about bacteriostatics"):** Erythromycin (macrolides), Clindamycin, Sulfonamides, Trimethoprim, Tetracyclines, Chloramphenicol.

**PK/PD relevance:** - Time-dependent killing (β-lactams, vancomycin): efficacy correlates with %T>MIC, the percentage of the dosing interval that free drug exceeds the MIC. Dosing strategies include frequent dosing or extended/continuous infusion. - Concentration-dependent killing (aminoglycosides, fluoroquinolones): efficacy correlates with Cmax/MIC. Once-daily high-dose regimens are used, and these drugs have a post-antibiotic effect. - AUC/MIC (fluoroquinolones, vancomycin, azithromycin, tetracyclines): efficacy correlates with total drug exposure.

**Clinical significance:** - Used to choose therapy for serious infections (bacteremia, endocarditis, meningitis), for resistant organisms (MRSA, VRE, ESBL, CRE), and for fungal and mycobacterial susceptibility testing. - Rising MIC ("MIC creep") may precede frank resistance. An example is vancomycin MIC ≥2 in MRSA, which is associated with treatment failure. Penicillin MIC in S. pneumoniae determines the breakpoint, which differs for meningitis and non-meningitis infections. - Combination therapy synergy is assessed with the checkerboard assay, which gives the FIC index.

**Pitfalls:** - The MIC is measured in vitro and doesn't account for host immunity, protein binding, biofilms, abscess pH, or inoculum effect (a high bacterial load raises the MIC). - It cannot be compared across drugs or organisms without breakpoints.

**Don't confuse with (other "MIC" abbreviations):** - **Mycobacterium intracellulare complex**, part of Mycobacterium avium complex (MAC). It is sometimes abbreviated MAI. - **MIC (Microscopic Immune Complex)** is not standard for boards. - **Myocardial infarction** is abbreviated MI, not MIC.