다제내성 Acinetobacter baumannii에 대한 C12-prp 펩타이드의 항생효과 평가

Abstract

Background: Given the limitations of monotherapy for Extensively drug resistant (XDR) A. baumannii strains, urgent need to find out new treatment options such as combination regimen of antibiotics and peptide useful for microbial eradication in patients infected with XDRab strains. we evaluated antimicrobial activity of peptide- antibiotics combinations against XDR A. baumannii clinical isolates. Materials and methods: Twenty-five clinical isolates of extensively drug resistant (XDR) A. baumannii were used in this study. Antimicrobial susceptibility results obtained by VITEKⅡ system were used to select XDR A. baumannii. We determined minimum inhibitory concentration (MIC) of antimicrobials used for time-kill assay by broth microdilution method. We used multiple-combination bactericidal test (MCBT) to select effective antibiotic candidates among 8 antibiotics including ceftazdime, cepefime, ciprofloxacin, colistin, doxycycline, meropenem, rifampicin, tigecycline. Then we performed time-kill assay of selected peptide-antibiotics combinations to determine synergy rate of each combination. We used two criteria (criteria 1 and 2) for definition of synergy. The criteria 1 for synergism was defined as ≥2 log10 CFU/mL reduction with the combination compared with the most active single agent. The criteria 2 for synergism was defined as ≥2 log10 CFU/mL reduction with the combination compared with the most active single agent and ≥2 log10 CFU/mL reduction below the initial inoculum at 24 hr. Result: Among 7 combination of peptide-antibiotics, 3 combination of c12-prp [peptide] + colistin, peptide + rifampicin and peptide + tigecyclin showed higher synergy rate than other combinations. The synergy rates of colistin + C12-prp combination was 96% by synergy criteria 2. the synergy rates of tigecycline + C12-prp combination and rifampicin + C12-prp combination were 100% by criteria 1 and 2 using time-kill assay. c rate of colistin + c12-prp combination, tigecycline + C12-prp combination, and rifampicin + C12-prp combination were 96%, 100%, and 92%, respectively. Conclusion: Because the rates of c and bactericidality were very high in colistin + C12-prp combination, tigecycline + C12-prp combination, and rifampicin + C12-prp combination, these combinations might be the good candidates for in vivo assessment of antimicrobial effect.