minimum inhibitory concentration

**Definition & method** - MIC = lowest antimicrobial concentration that inhibits visible growth of an organism (typically after 16-24 h incubation). - Determined by broth dilution (macro- or microdilution), agar dilution, gradient diffusion (E-test), or automated systems (e.g., Vitek, MicroScan). Serial two-fold dilutions of drug are inoculated with a standardized inoculum; the first clear tube/well is the MIC. - Kirby-Bauer disk diffusion is a qualitative/semi-quantitative method: the zone of inhibition diameter is inversely related to MIC. It does not give a direct MIC.

**Interpretation** - MIC is compared with clinical breakpoints (CLSI/EUCAST) to report S (susceptible), I (intermediate/susceptible-dose dependent), or R (resistant). - Breakpoints are based on PK/PD, achievable serum/tissue levels, microbiological data, and clinical outcomes. - A lower MIC does not mean a drug is "better" than another with a higher MIC. Each drug has its own breakpoint, and MICs can't be directly compared across drugs. - MIC50/MIC90 = concentrations that inhibit 50%/90% of isolates in a population; these are used in surveillance.

**Related terms** - **MBC (minimum bactericidal concentration):** lowest concentration that kills ≥99.9% (3-log reduction) of the initial inoculum. It's determined by subculturing from clear MIC wells onto drug-free media. - A drug is considered bactericidal if MBC:MIC ≤4 and bacteriostatic if the ratio is >4. Tolerance occurs when the MBC is much greater than the MIC (e.g., vancomycin against tolerant staphylococci/enterococci). - **Post-antibiotic effect (PAE):** persistent suppression of growth after drug levels fall below the MIC (e.g., aminoglycosides, fluoroquinolones). - **Sub-MIC effects** and **mutant prevention concentration (MPC)** are related to resistance selection.

**PK/PD correlates (high-yield for therapy)** - **Time-dependent killing** (β-lactams, vancomycin [AUC-dependent], macrolides, clindamycin): the best predictor is %fT>MIC, the percentage of the dosing interval that free drug exceeds the MIC. This favors extended or continuous infusions. - **Concentration-dependent killing** (aminoglycosides, fluoroquinolones, daptomycin, metronidazole): the best predictors are Cmax/MIC and AUC/MIC. This favors high-dose, once-daily dosing, and these drugs have a PAE. - **AUC/MIC:** fluoroquinolones, vancomycin, azithromycin, tetracyclines.

**Clinical significance** - Guides drug selection and dosing, especially for serious infections (bacteremia, endocarditis, meningitis), where tissue penetration matters. - Detects emerging resistance. "MIC creep" refers to a gradual rise in MIC within the susceptible range (e.g., vancomycin against MRSA). - Resistance mechanisms (β-lactamases, altered PBPs such as PBP2a/mecA, efflux pumps, target mutation) raise the MIC. - Limitations: it's an in vitro test, it doesn't account for host factors, protein binding, the site of infection, biofilms, or the inoculum effect, and it measures inhibition, not killing. Immunocompromised patients and endocarditis often need bactericidal therapy.

**Test-taking pearls** - "Lowest concentration that prevents visible growth" → MIC. - "Lowest concentration that kills 99.9%" → MBC. - Larger zone of inhibition on disk diffusion = lower MIC = more susceptible. - Lower MIC ≠ more effective drug when comparing different agents.