FDA Rationale for Recognition Decision: Colistimethate

FDA has reviewed the published literature and the CLSI Rationale Document that includes target attainment estimation used in determining the PK/PD targets for colistin against P. aeruginosa and A. baumannii. Results of these analyses do not support the proposed S/R breakpoints of ≤2 μg/mL Susceptible, ≥4 μg/mL Resistant for colistin against these bacteria because the percent target attainment at 2 μg/mL is predicted to be substantially lower than 90%, ranging from 22 to 78% depending on renal function. Based on the PK/PD assessments provided, we conclude that the proposed susceptible breakpoints for colistin against P. aeruginosa and A. baumannii are not supported considering the PK/PD target values obtained from the lung infection model.