Limitations of antimicrobial agent choice based on MIC value against Pseudomonas aeruginosa

<b>Introduction.</b> In antibiotic chemotherapy, an antimicrobial agent is selected based on MIC, which is determined by a test method using the principle of the broth microdilution. However, it does not provide a viable count in the mutant selection window. In this study, we used turbidimetry and visual judgement to examine the validity of the selection of various antibiotics to treat <i>Pseudomonas aeruginosa</i> based on MIC determination after 24 h of incubation.<b>Methods.</b> The antibiotics used in this study were piperacillin (PIPC), imipenem (IPM), meropenem, ciprofloxacin and amikacin (AMK). The strains used were 30 <i>P</i>. <i>aeruginosa</i> strains clinically isolated that were susceptible to all the antibiotics used, and the standard PAO1 strain. The viable count was measured after exposure for 3 and 24 h to therapeutic concentrations of various antibiotics, at which time turbidity was examined visually or by transmittance. In addition, the MPCs of IPM and PIPC were measured.<b>Results.</b> In this study, 10²-10⁸ c.f.u. ml^-1 of <i>P. aeruginosa</i> survived exposure to PIPC, IPM and AMK at concentrations 2.5-80 times the MIC despite high drug concentrations. No turbidity was observed in the culture medium. Furthermore, both IPM and PIPC showed high mutant prevention concentration (MPC), with 64.5% of strains in IPM and 10% of strains in PIPC showing intermediate or resistance after 24 h.<b>Conclusions.</b> Choosing an appropriate antibiotic based on exceeding the MIC may be insufficient. While the PK/PD theory focuses on MIC, measuring MPC alongside MIC is urgent in clinical practice for optimal antibiotic selection.