Question 6

In addition to the above pharmacologic values, the concept of the mutant prevention concentration (MPC) has been suggested as useful for guiding the most appropriate use of antimicrobials. Could you discuss the role of MPC in determining fluoroquinolone treatment regimens?

The mutant prevention concentration (MPC) is an in vitro parameter derived from PK/PD and MIC data and is used to evaluate the activity of a drug and its potential for preventing resistance. The MPC is defined as the minimum concentration that inhibits growth of first-step mutants and is the MIC that prohibits growth of mutants from a susceptible population of more than 10^-9 cells (7). In addition, the mutant selection window (MSW) is the concentration range of an antimicrobial from the MIC required to block growth up to the MPC. In the clinical situation, we can use the MIC to demonstrate whether a pathogen is susceptible or resistant. In contrast, the MPC is a concept that demonstrates the probability of a pathogen to develop a resistant mutant. These determinations can be used to compare different drugs under differing conditions and to establish dose schedules but is not used in individual clinical situations.

By using the MPC value alongside an agent’s PK profile it is believed that dosing regimens can be optimized to prevent the emergence of resistance. Results indicate that higher values of AUC_0-24/MPC and C_max/MPC are associated with reduced S. pneumoniae resistance (3).