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The mutant prevention concentration (MPC) offers a novel approach for the treatment of infectious diseases31. Essentially, the MPC-approach favours a dose selection that not only aims at clinical cure but also at reducing selection of bacterial resistance.

Bacterial populations naturally contain resistant variants (mutants). The minimum inhibitory concentration (MIC) of an antimicrobial defines the susceptibility of a bacterial isolate, while the mutant prevention concentration (MPC) determines the drug concentration needed to inhibit the least susceptible first step resistant mutant that can develop from this isolate.

The mutant selection window (MSW) is the drug concentration range between the MIC and the MPC. When drug concentrations are below the MIC, there is no selective pressure for the bacterial population, and at drug concentrations above the MPC, the entire bacterial population including resistant variants is inhibited. Thus, no resistant mutants will be selected in either situation. However, if drug concentrations fall into the MSW for prolonged times, resistant mutants are likely to develop.

Mutant Prevention Concentration (MPC) and Mutant Selection Window (MSW)32

In the treatment of bacterial infections, concentrations above the MPC at the site of infection can prevent selection of resistant mutants. However, current dosing recommendations focus on the MIC or multiples of the MIC rather than MPC. Since prior strategies have failed to slow the progression of bacterial resistance to antimicrobials, novel approaches for dealing with resistance are required.

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