- 作者: Jeongwoo Jo, Ki Tae Kwon & Kwan Soo Ko
- 作者服務機構: 1.Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea 2.Department of Microbiology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea
- 中文摘要:
- 英文摘要:
Background We investigated the presence of heteroresistance against both tigecycline and colistin in Acinetobacter
baumannii and then evaluated the efectiveness of combined antibiotic treatment given the existence of discrete
tigecycline- and colistin-resistant subpopulations.
Methods We performed population analysis profling (PAP) to evaluate the degree of composite heteroresistance in
A. baumannii isolates, with the extent of this resistance quantifed using subsequent antibiotic susceptibility testing.
We then evaluated the amino acid sequence of PmrBAC and the relative mRNA expression levels of pmrB. Finally, we
investigated the combined antibiotic efcacy of tigecycline and colistin in multiple-heteroresistant isolates using dual
PAP and in vitro time-killing assays.
Results All tigecycline-heteroresistant A. baumannii isolates, with the exception of one colistin-resistant isolate, were
also heteroresistant to colistin. Evaluations of the colistin-resistant subpopulations revealed amino acid alterations
in PmrA and PmrB and increased expression of pmrB. All tigecycline-resistant subpopulations were susceptible to
colistin, and all colistin-resistant subpopulations were susceptible to tigecycline. Dual PAP analysis using tigecycline
and colistin showed no heteroresistance, and in vitro time-killing assays revealed that a combination of these two
antibiotics efectively eliminated the bacterial cells.
Conclusion Our results suggest that multiple heteroresistance to tigecycline and colistin is highly prevalent among
A. baumannii clinical isolates and that these resistant subpopulations exist independently in single multiple heteroresistant isolates. Therefore, our fndings may explain the success of combined antibiotic therapies in these infections. - 中文關鍵字:
- 英文關鍵字: Acinetobacter baumannii, Tigecycline, Colistin, Multiple heteroresistance, Combination therapy