Zhong Yang, Teo Jocelyn Qi Min, Yi Chang Hong, Jiahao Yeo, Shuhua Thong, Sihui Tan, Yusoff Nurhayati Binte Monhamed, Peng Lim Tze, Kwa Andrea Lay Hoon
Department of Clinical TranslaCtional Research, Singapore General Hospital, Singapore; Pharmacy, Singapore General Hospital, Singapore.
Pharmacy, Singapore General Hospital, Singapore.
J Glob Antimicrob Resist. 2025 Jul 22. doi: 10.1016/j.jgar.2025.06.021.
Eravacycline (ERV), a novel tetracycline-class antibiotic, has demonstrated efficacy against carbapenem-resistant Acinetobacter baumannii (CRAB) in Europe and the USA but has not been evaluated in Singapore. The objectives of this study are to evaluate the activity of ERV against CRAB clinical isolates from Singapore and to investigate the genetic profiles of these isolates, exploring novel potential ERV resistance mechanisms through whole genome sequencing (WGS) analysis.
Three hundred CRAB clinical isolates collected from Singapore General Hospital (SGH) between 2012 and 2021 were tested for their susceptibility to ERV and other antibiotics. The genomic profile, including sequence type (ST), antimicrobial resistance (AMR), and virulence factor (VF) genes of these isolates, was determined. Isolates exhibiting high ERV MICs were further analyzed to identify potential genetic mutations associated with reducing ERV susceptibility.
ERV demonstrated strong in vitro activity against CRAB, with an MIC of 2 µg/mL. WGS analysis revealed that the 300 CRAB isolates belonged to 23 STs, with ST2 being the predominant population and frequently harbouring intrinsic bla-type β-lactamases and tetracycline-class efflux pumps (tet(B)). VF analysis showed extensive genetic diversity, with variations beyond simple presence/absence patterns. Notably, the emergence of ERV resistance (elevated MIC, MIC > MIC) was detected, and genetic analysis of high-MIC isolates identified novel mutations in the resistance-nodulation-cell division (RND) efflux pump genes (adeABC, adeFGH, and adeIJK) and their regulatory elements (adeS/R and adeL/N).
ERV is a promising therapeutic option for managing CRAB infections in Singapore. However, the emergence of resistance mediated by novel genetic mutations highlights the need for continuous surveillance and further investigation.
依拉环素（ERV）是一种新型四环素类抗生素，在欧洲和美国已显示出对耐碳青霉烯鲍曼不动杆菌（CRAB）有效，但尚未在新加坡进行评估。本研究的目的是评估依拉环素对来自新加坡的CRAB临床分离株的活性，并调查这些分离株的基因特征，通过全基因组测序（WGS）分析探索新的潜在依拉环素耐药机制。
对2012年至2021年间从新加坡总医院（SGH）收集的300株CRAB临床分离株进行依拉环素和其他抗生素的敏感性测试。确定这些分离株的基因组特征，包括序列类型（ST）、抗菌药物耐药性（AMR）和毒力因子（VF）基因。对依拉环素最低抑菌浓度（MIC）较高的分离株进行进一步分析，以鉴定与依拉环素敏感性降低相关的潜在基因突变。
依拉环素对CRAB显示出强大的体外活性，MIC为2μg/mL。WGS分析显示，300株CRAB分离株属于23种ST，其中ST2是主要群体，且经常携带固有bla型β-内酰胺酶和四环素类外排泵（tet(B)）。VF分析显示出广泛的遗传多样性，其变异超出了简单的存在/缺失模式。值得注意的是，检测到依拉环素耐药性的出现（MIC升高，MIC＞MIC），对高MIC分离株的基因分析确定了耐药结节化细胞分裂（RND）外排泵基因（adeABC、adeFGH和adeIJK）及其调控元件（adeS/R和adeL/N）中的新突变。
依拉环素是新加坡治疗CRAB感染的一种有前景的治疗选择。然而，新基因突变介导的耐药性的出现凸显了持续监测和进一步研究的必要性。
