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Importance of minimum inhibitory concentration (MIC) values.

Some pathology laboratories are currently reporting minimum inhibitory concentration (MIC) values on antimicrobials in addition to the susceptible, intermediate and resistant category results.

The MIC of an isolate is the lowest concentration of an antimicrobial agent that prevents visible growth of that particular micro-organism in an agar or a broth-dilution susceptibility test. The susceptible, intermediate and resistant interpretative categories are based on extensive studies correlating MICs with achievable serum levels for each antimicrobial agent, particular resistance mechanisms and successful therapeutic outcomes.

The MIC can guide the choice of antimicrobial used in treatment by predicting efficacy. If pharmacokinetic and pharmacodynamic (PKPD) principles are met by careful selection of a specific antimicrobial given at an appropriate dosage, it will lead to clinical cure, eradication of carrier status of a specific organism, and prevention of selection of resistance.

The interpretation of MICs requires an understanding of the mode of activity of the different antimicrobial classes.

Antimicrobials can be classified according to time-dependent or concentrationdependent activity. Beta-lactam antimicrobials have time-dependent activity, whereas quinolones and aminoglycosides have concentration-dependent activity.

Time-dependent antimicrobials

With beta-lactam antimicrobials the goal of treatment is to maximise the time that the free serum concentration of the drug exceeds the MIC (T>MIC), with killing of bacteria being optimal at 4 - 5 times the MIC in vitro. There is a correlation between the duration of the antimicrobial concentration exceeding the MIC, and the time it takes to eradicate the pathogen. If beta-lactam antimicrobials are administered by constant (most penicillins and cephalosporins) or extended (carbapenems) infusion, a prolonged duration above the MIC is achieved, which reduces the time to achieve bacterial eradication--especially in critically ill patients. (1) Some beta-lactams are not stable over time, e.g. amoxicillin and carbapenems; these antimicrobials cannot be infused constantly.

Concentration-dependent antimicrobials

For quinolones the goal of treatment is to maximise the achievable peak serum drug concentration ([C.sub.max]) in relation to the MIC. A [C.sub.max]:MIC ratio of 10 - 12 ensures clinical cure and prevents selection of resistance. The area under the plasma concentration versus time curve (AUIC):MIC ratio is another predictor of outcome in this class of antimicrobial. When treating Gram-negative infections, maximum efficacy is achieved when AUIC:MIC values are in the region of 100 -125. Lower values may relate to less rapid bactericidal activity and development of resistance. Although an antimicrobial with a low AUIC value may still lead to clinical cure, a higher value will also eradicate carrier status and will be less likely to select resistance.

Both T>MIC and AUIC values are directly dependent on the MIC value, and dosing should be optimised according to these values. (2) When selecting an antimicrobial with the lowest MIC in a specific class, the chances will improve that target PKPD values are achieved. It is important to note that a low MIC value for a specific class of antimicrobial cannot necessarily be compared with a low value for another class.

MARTHINUS SENEKAL, MB ChB, MMed Micro Path

Clinical Microbiologist, Pathcare, Goodwood

Correspondence to: Marthinus Senekal (senekal@pathcare.co.za)

References

(1.) Mouton JW, Vinks AA. Continuous infusion of beta-lactams. Curr Opin Crit Care 2007; 13(5): 598-606.

(2.) Legget JE, Ebert S, Fantin B, Graig WA. Comparative dose-effect relations at several dosing intervals for beta-lactam, aminoglycoside and quinolone antibiotics against Gram-negative bacilli in murine thigh infection and pneumonitis models. Scan J Infect Dis Suppl 1990; 74: 179-184.
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Title Annotation:More about ... Bacterial diseases
Author:Senekal, Marthinus
Publication:CME: Your SA Journal of CPD
Article Type:Report
Geographic Code:6SOUT
Date:Jun 1, 2010
Words:567
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