Mutant prevention concentration of polymixin B for the clinical isolates of multi-drug resistant Pseudomonas aeruginosa

Abstract

The increasing prevalence of multi-drug resistant non-fermenting gram-negatives such as Pseudomonas aeruginosa or Acinetobacter spp. has revived the interest in polymyxins, a bactericidal antibiotic that was used in the 1960s. The mutant prevention concentration (MPC) is the drug level that inhibits first-step mutants against the clinical selection. Although polymyxins have not been used wide recently, there have been several reports for the resistance development in Pseudomonas or Acinetobacter spp. In order to estimate the probability of resistance development of polymyxins, we determined the MICs and MPCs of polymyxin B and compared those values with the ciprofloxacin for the 30 clinical isolates of multi-drug resistant but ciprofloxacin-sensitive P. aeruginosa. The MIC50 and MIC90 values of polymyxin B were 1 and 2 mg/L and the MPC50 and MPC90 values were 32 and 64 mg/L, respectively. MIC50 and MIC90 values of ciprofloxacin for those strains were <0.25 and 1 mg/L, and MPC50 and MPC90 values of ciprofloxacin were 6 and 16 mg/L, respectively. The frequency of mutant selection of the polymyxin B in P. aeruginosa was 10-7 to 5x 10-9. Although the pharmacokinetic parameters of polymyxin B were not clearly studied, when comparing the MPC with the drug level in serum (Cmax 8mg/L), it can be seen that polymyxin B develop resistance considerably.