Impact of Two-Component Regulatory Systems PhoP-PhoQ and PmrA-PmrB on Colistin Pharmacodynamics in Pseudomonas aeruginosa

The in vitro pharmacodynamics of colistin against Pseudomonas aeruginosa PAO1 wild-type and isogenic knockout strains of phoP and pmrA were evaluated. Colistin killing at subinhibitory concentrations was greater against the phoP and pmrA mutants than the wild type within the first 8 h: the concentration that results in 50% of maximal effect (EC50) of the pmrA mutant (0.413 mg/liter) was less than that of the wild type (0.718 mg/liter) (P < 0.05). An in vitro pharmacodynamic model simulating human colistin regimens displayed initial killing followed by regrowth in the phoP mutant and gradual regrowth in the pmrA mutant and wild type.