Tigecycline heteroresistance and resistance mechanism in clinical isolates of Acinetobacter baumannii

Tigecycline is regarded as a last-resort treatment for multidrug-resistant Acinetobacter baumannii. However, tigecycline resistance in A. baumannii has increased worldwide. In this study, we investigated heteroresistance isolates from South Korea. Antibiotic susceptibility testing was performed on 323 nonduplicated isolates. Among 260 and 37 tigecycline-susceptible -intermediate-resistant isolates, 146 (56.2%) 22 (59.5%) were identified heteroresistant to through disk diffusion assay population analysis profiling. For selected an vitro time-kill performed, survival rates measured after preincubation with diverse concentrations of tigecycline. Heteroresistant showed regrowth 12 h 2× MIC treatment, resistant subpopulations by preexposure Furthermore, genetic alterations adeABC, adeRS, rpsJ assessed, the relative mRNA expression levels adeB adeS compared. The might be due insertion ISAba1 adeS, leading overexpression AdeABC efflux pump. not stable during serial passages antibiotic-free medium. reversion occur additional insertions ISAba10 adeR nucleotide some mutants. prevalent which results failure. mainly pump, associated mutations, but could reversed into mutations environments. IMPORTANCE evidence that antibiotic responsible failure clinical settings increasing. Thus, detection characterization would important appropriate therapeutic guidance treat bacterial infections. data Gram-negative bacteria currently limited, although last-line against infections caused antibiotic-resistant pathogens. baumannii, been listed WHO priority research development new antibiotics. We found very high prevalence tigecycline-heteroresistant may result selection subpopulations. also main mechanism tigecycline-resistant subpopulations, is, upregulation pumps adeS.