ScholarWorks@성균관대학교

초록

Background Our research aimed to investigate the potential of in vitro triple antimicrobial synergism against carbapenem-resistant Pseudomonas aeruginosa (CRPA) as a strategy to overcome antimicrobial resistance.Methods We used 12 CRPA blood isolates stocked in the Asian Bacterial Bank between 2016 and 2018. All isolates were tested by multi-locus sequencing and carbapenemase multiplex PCR. To assess the antimicrobial interactions, we performed time-kill assays using double or triple combination regimens. These regimens included CST and/or rifampin combined with IPM, MEM, or CZA. The assay was conducted at 1x and 0.5x MICs.Results Among the 12 CRPA isolates, nine produced metallo-beta-lactamases (6 IMP-6, 2 VIM-2 and 1 NDM-1). In the time-kill assay, the median viable bacterial count for CST-rifampin was the lowest among double combinations after 24 h incubation (2.25 log cfu/mL at 1x MIC and 3.71 log cfu/mL at 0.5x MIC). In contrast, all triple combinations achieved 0 log cfu/mL at both 1x MIC and 0.5x MIC. Compared with CST-rifampin (synergism: 25% at 1x MIC, 42% at 0.5x MIC; bactericidal: 50% at 1x MIC, 42% at 0.5x MIC), all triple combinations showed greater synergism and bactericidal activity at both 1x MIC (50%-75% for synergism, 75%-83% for bactericidal activity) and 0.5x MIC (58%-75% for both).Conclusions Our findings suggest that CST-rifampin-based triple antimicrobial combinations exhibit greater synergy and bactericidal activity in eradicating CRPA compared with double antimicrobial combinations.

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