Department of Pharmacy, Singapore General Hospital, Singapore, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
Emerg Microbes Infect. 2021 Dec;10(1):1706-1716. doi: 10.1080/22221751.2021.1968318.
is a clinically important pathogen implicated in many hospital-acquired infections. Its propensity to acquire broad-spectrum resistance has earned the organism its status as a severe public health threat requiring urgent control measures. While whole-genome sequencing-based genomic surveillance provides a means to track antimicrobial resistance, its use in molecular epidemiological surveys of remains limited, especially in the Southeast Asian region. We sequenced the whole genomes of 222 carbapenem-non-susceptible (CNPA) isolates collected in 2006-2020 at the largest public acute care hospital in Singapore. Antimicrobial susceptibilities were determined using broth microdilution. Clonal relatedness, multi-locus sequence types, and antimicrobial resistance determinants (acquired and chromosomal) were determined. In this study, CNPA exhibited broad-spectrum resistance (87.8% multi-drug resistance), retaining susceptibility only to polymyxin B (95.0%) and amikacin (55.0%). Carbapenemases were detected in 51.4% of the isolates, where IMP and NDM metallo--lactamases were the most frequent. Carbapenem resistance was also likely associated with OprD alterations or efflux mechanisms (ArmZ/NalD mutations), which occurred in strains with or without carbapenemases. The population of CNPA in the hospital was diverse; the 222 isolates grouped into 68 sequence types (ST), which included various high-risk clones. We detected an emerging clone, the NDM-1-producing ST308, in addition to the global high-risk ST235 clone which was the predominant clone in our population. Our results thus provide a "snapshot" of the circulating lineages of CNPA locally and the prevailing genetic mechanisms contributing to carbapenem resistance. This database also serves as the baseline for future prospective surveillance studies.
是一种临床上重要的病原体,与许多医院获得性感染有关。其广泛获得广谱耐药性的倾向使其成为严重的公共卫生威胁,需要采取紧急控制措施。虽然基于全基因组测序的基因组监测提供了一种追踪抗微生物药物耐药性的方法,但它在 的分子流行病学调查中的应用仍然有限,特别是在东南亚地区。我们对 2006 年至 2020 年在新加坡最大的公立急性护理医院收集的 222 株耐碳青霉烯类非敏感性 (CNPA)分离株进行了全基因组测序。使用肉汤微量稀释法测定抗微生物药物敏感性。确定克隆相关性、多位点序列类型和抗微生物药物耐药决定因素(获得性和染色体)。在这项研究中,CNPA 表现出广谱耐药性(87.8%的多药耐药性),仅对多粘菌素 B(95.0%)和阿米卡星(55.0%)保持敏感性。51.4%的分离株检测到碳青霉烯酶,其中 IMP 和 NDM 金属--内酰胺酶最为常见。碳青霉烯类耐药性也可能与 OprD 改变或外排机制(ArmZ/NalD 突变)有关,这些改变发生在有或没有碳青霉烯酶的菌株中。医院中 CNPA 的人群多种多样;222 株分离株分为 68 种序列类型(ST),其中包括各种高风险克隆。除了我们人群中主要流行的全球高风险 ST235 克隆外,我们还检测到了一种新出现的克隆,即产 NDM-1 的 ST308。我们的结果因此提供了本地 CNPA 循环谱系和导致碳青霉烯类耐药性的主要遗传机制的“快照”。该数据库还作为未来前瞻性监测研究的基线。