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| CHALLENGES & NEW DEVELOPMENTS IN CANINE PYODERMA
THE THREE Ms: MIC, MPC, & MSW Mean inhibitory concentration (MIC) is usually based on blood levels of an antibiotic, and is the minimal antibiotic concentration needed to inhibit bacterial growth. When the MIC exceeds the concentration of drug that can be safely achieved in the bloodstream, then the organism is deemed resistant.
Bacterial Mutation & Resistance MIC is based on standardized bacterial inoculums (105
CFU/mL) exposed to varying drug
concentrations in a test tube, and it varies with both the drug and the bacterial species targeted. r 4JODF .*$ EPFT OPU FRVBM DPNQMFUF LJMMJOH PG BMM CBDUFSJB CBDUFSJBM NVUBUJPO BOE SFTJTUBODF JT B concern.
r Patients with normal intact immune systems: Inhibition of the susceptible bacterial population allows immune clearance of infection, including resistant mutants.
r Immunocompromised patients, those with prior infection or previous exposure to antibiotics, or those in which therapy for acute infection fails: Continued proliferation of resistant mutants may occur.
r 8IFO B IJHI EFOTJUZ CBDUFSJBM QPQVMBUJPO JT FYQPTFE UP BO BOUJNJDSPCJBM BHFOU JU POMZ SFRVJSFT one spontaneous mutation to the exposed agent for the culture to become a > 1012
population of resistant bacteria following overnight incubation.1
Measuring Mutant Prevention Recently, the mutant prevention concentration (MPC) has been described as a novel measurement of in vitro bacterial susceptibility or resistance. MPC defines the lowest drug concentration required to block the growth of the least susceptible bacterium present in the tested population. MPC is based on the testing of a larger bacterial inoculum (≥ 109 CFU/mL), which:
r .PSF DMPTFMZ BQQSPYJNBUFT CBDUFSJBM MPBE JO BDUVBM JOGFDUJPOT r 5BLFT JOUP BDDPVOU UIF QSPCBCJMJUZ PG NVUBOU TVCQPQVMBUJPOT CFJOH QSFTFOU JO IJHI EFOTJUZ CBDUFSJBM QPQVMBUJPOT 1,2 Dosing based on MPC drug concentration may reduce overall
bacterial numbers as well as prevent the selective amplification of the resistant subpopulation. As with MIC, MPC varies with both the antimicrobial and bacterial species targeted.
Minimizing Mutation Development The mutant selection window (MSW) defines the danger zone for therapeutic drug concentrations, and is bordered by the MIC and the MPC values. Minimizing the length of time UIBU BO BOUJCJPUJD DPODFOUSBUJPO SFNBJOT JO UIF .48 NBZ SFEVDF UIF MJLFMJIPPE GPS EFWFMPQNFOU PG resistance during therapy.
Achieving Optimal Antibiotic Dosing MPC values, when considered with antimicrobial pharmacology, may allow more accurate prediction of probability of resistance when bacteria are exposed to antibiotics during therapy for infectious diseases. With the increasing emergence of resistant infections, resistance prevention should be an important goal of antimicrobial therapy. Hopefully, MPC and MSW values may eventually become more widely available from reference laboratories and allow for optimal antibiotic dosing, reducing antimicrobial resistance.
CFU = colony forming units; MIC = mean inhibitory concentration; MPC = mutant prevention concentration; MSW = mutant selection window
1. Blondeau J. New concepts in antimicrobial susceptibility testing: The mutant prevention concentration and mutant selection window approach. Vet Derm 2009; 20:383-396.
2. Xilin Zhao X, Drlica K. Restricting the selection of antibiotic-resistant mutants: A general strategy derived from fluoroquinolone studies. Clin Infect Dis 2001; 33(3):S147–S156.
3. White SD. Review article: Systemic treatment of bacterial skin infections of dogs and cats. Vet Derm 1996; 7:133-143.
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Today's Veterinary Practice January/February 2012