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Minimum inhibitory concentration

In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical which prevents visible growth of a bacterium. This is in difference to the minimum bactericidal concentration (MBC) which is the concentration resulting in microbial death as defined by the inability to re-culture bacteria. The closer the MIC is to the MBC, the more bactericidal the compound.[1]

The MIC of a chemical is determined by preparing solutions of the chemical in vitro at increasing concentrations, incubating the solutions with the separate batches of cultured bacteria, and measuring the results using agar dilution or broth microdilution. Results have been graded into susceptible (often called sensitive), intermediate, or resistant to a particular antibiotic by using a cut off point. Cut off points are agreed upon values, published in guidelines of a reference body, such as the U.S. Clinical and Laboratory Standards Institute (CLSI), the British Society for Antimicrobial Chemotherapy (BSAC) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST).[2].

A MIC depends on the microorganism, the affected human being (in vivo only), and the antibiotic.[3]

These in vitro MICs are based on concentrations of antibiotics obtained in vivo (ie, in blood, serum, or CSF). However, these in-vivo concentrations depend on arbitrary administered doses. General antibiotic MIC guidelines have been imposed on the basis of a consensus of the influence of main instigators (ie, politicians and pharmaceutical companies).

There have been major discrepancies between the recommendations from various European countries over the years, and between those from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the US Clinical and Laboratory Standards Institute (CLSI). [4]

In medicine, culturing the organism infecting a patient with available antibiotic drugs and determining the MICs, is important to identify the correct drug to administer to the patient.[2][5]

The first step in drug discovery is often the screening of a library drug candidate for MICs against bacteria of interest.[6] As such, MICs are usually the starting point for larger preclinical evaluations of novel antimicrobial agents.[7]

Minimum Inhibitory Concentration: Tube Dilution Assay is performed by constantly increasing the percent concentration of antimicrobial agent to microbial rich broth in a series of tubes. It is used to measure the Minimum Inhibitory Concentration [MIC] of an antimicrobial agent, which is the lowest concentration of antimicrobial agent which will inhibit the growth of microbes. The turbidity of the tubes indicates the amount of microbe growth, with the least turbid, or clear, tubes (tubes 6 and 7) correlating with the absence of microbes. The tube with no antimicrobial agent (tube 1) presents as opaque and most turbid because the microbes are able to flourish. As antimicrobial concentration increases, the turbidity decreases until the MIC is reached and microbes can no longer survive. Antimicrobials with low MICs are more effective than those with high MICs, as only a low dosage is necessary to eradicate microbes.

References

  1. ^ Tripathi, K.D. (2013). Essentials of Medical Pharmacology (7th ed.). New Delhi, India: Jaypee Brothers Medical Publishers. pp. 696,697. 
  2. ^ a b Andrews, J. M. (1 July 2001). "Determination of minimum inhibitory concentrations". Journal of Antimicrobial Chemotherapy. 48 (suppl 1): 5–16. doi:10.1093/jac/48.suppl_1.5. PMID 11420333. 
  3. ^ McKinnon, PS and Davis, SL. Pharmokinetic and pharmacodynamic issues in the treatment of bacterial infectious diseases. in: VL Yu, G Edwards, PS McKinnon, C Peloquin, G Morse (Eds.) Antimicrobial therapy and vaccines, volume II: antimicrobial agents. ESun Technologies, Pittsburgh, PA; 2005: 5–19
  4. ^ Seydina M Diene, Cédric Abat, Jean-Marc Rolain, Didier Raoult. How artificial is the antibiotic resistance definition? Lancet Infectious Diseases, Volume 17, No. 7, p690, July 2017. DOI: [dx.doi.org]
  5. ^ Yamamoto, Loren G. (February 2003). Chapter VI.4. Inhibitory and Bactericidal Principles (MIC & MBC). Case Based Pediatrics For Medical Students and Residents, University of Hawaii John A. Burns School of Medicine
  6. ^ Turnidge JD, Ferraro MJ, Jorgensen JH (2003) Susceptibility Test Methods: General Considerations. In PR Murray, EJ Baron, JH Jorgensen, MA Pfaller, RH Yolken. Manual of Clinical Microbiology. 8th Ed. Washington. American Society of Clinical Microbiology. p 1103 ISBN 1-55581-255-4
  7. ^ O'Neill, AJ; Chopra, I (August 2004). "Preclinical evaluation of novel antibacterial agents by microbiological and molecular techniques". Expert Opinion on Investigational Drugs. 13 (8): 1045–63. doi:10.1517/13543784.13.8.1045. PMID 15268641.