Pham My H, Hoi Le Thi, Beale Mathew A, Khokhar Fahad A, Hoa Nguyen Thi, Musicha Patrick, Blackwell Grace A, Long Hoang Bao, Huong Dang Thi, Binh Nguyen Gia, Co Dao Xuan, Giang Tran, Bui Cuong, Tran Hai Ninh, Bryan James, Herrick Archie, Feltwell Theresa, Nadjm Behzad, Parkhill Julian, van Doorn Hindrik Rogier, Trung Nguyen Vu, Van Kinh Nguyen, Török Mili Estée, Thomson Nicholas R
Wellcome Sanger Institute, Hinxton, UK; Oxford University Clinical Research Unit, Hanoi, Viet Nam.
National Hospital for Tropical Diseases, Hanoi, Viet Nam; Hanoi Medical University, Hanoi, Viet Nam.
Lancet Microbe. 2023 Apr;4(4):e255-e263. doi: 10.1016/S2666-5247(22)00338-X. Epub 2023 Feb 16.
Patients with prolonged hospitalisation have a significant risk of carriage of and subsequent infection with extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing Klebsiella pneumoniae. However, the distinctive roles of the community and hospital environments in the transmission of ESBL-producing or carbapenemase-producing K pneumoniae remain elusive. We aimed to investigate the prevalence and transmission of K pneumoniae within and between the two tertiary hospitals in Hanoi, Viet Nam, using whole-genome sequencing.
We did a prospective cohort study of 69 patients in intensive care units (ICUs) from two hospitals in Hanoi, Viet Nam. Patients were included if they were aged 18 years or older, admitted for longer than the mean length of stay in their ICU, and cultured K pneumoniae from their clinical samples. Longitudinally collected samples from patients (collected weekly) and the ICU environment (collected monthly) were cultured on selective media, and whole-genome sequences from K pneumoniae colonies analysed. We did phylogenetic analyses and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K pneumoniae.
Between June 1, 2017, and Jan 31, 2018, 69 patients were in the ICUs and eligible for inclusion, and a total of 357 K pneumoniae isolates were cultured and successfully sequenced. 228 (64%) of K pneumoniae isolates carried between two and four different ESBL-encoding and carbapenemase-encoding genes, with 164 (46%) isolates carrying genes encoding both, with high minimum inhibitory concentrations. We found a novel co-occurrence of bla and bla in 46·6% of samples from the globally successful ST15 lineage. Despite being physically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes.
These results highlight the high prevalence of ESBL-positive carbapenem-resistant K pneumoniae in ICUs in Viet Nam. Through studying K pneumoniae ST15 in detail, we showed how important resistance genes are contained within these strains that are carried broadly by patients entering the two hospitals directly or through referral.
Medical Research Council Newton Fund, Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and National Institute for Health and Care Research Cambridge Biomedical Research Centre.
住院时间延长的患者携带产超广谱β-内酰胺酶（ESBL）和产碳青霉烯酶的肺炎克雷伯菌并随后发生感染的风险很高。然而，社区和医院环境在产ESBL或产碳青霉烯酶肺炎克雷伯菌传播中的独特作用仍不明确。我们旨在利用全基因组测序调查越南河内两家三级医院内及医院间肺炎克雷伯菌的流行情况和传播情况。
我们对越南河内两家医院重症监护病房（ICU）的69例患者进行了一项前瞻性队列研究。纳入年龄在18岁及以上、住院时间超过其所在ICU平均住院时间且临床样本培养出肺炎克雷伯菌的患者。对患者纵向采集的样本（每周采集）和ICU环境样本（每月采集）在选择性培养基上进行培养，并对肺炎克雷伯菌菌落的全基因组序列进行分析。我们进行了系统发育分析，并将表型抗菌药物敏感性试验与肺炎克雷伯菌分离株的基因型特征相关联。我们构建了患者样本的传播网络，将ICU入院时间和地点与感染的肺炎克雷伯菌的基因相似性联系起来。
在2017年6月1日至2018年1月31日期间，69例患者入住ICU并符合纳入标准，共培养并成功测序了357株肺炎克雷伯菌分离株。228株（64%）肺炎克雷伯菌分离株携带2至4种不同的ESBL编码基因和碳青霉烯酶编码基因，164株（46%）分离株同时携带这两种基因，且最低抑菌浓度较高。我们在全球流行的ST15菌系46.6%的样本中发现了bla和bla的新共现情况。尽管两家医院在物理和临床方面相互隔离，但它们共享携带相同抗菌药物耐药基因阵列的密切相关菌株。
这些结果突出了越南ICU中产ESBL的耐碳青霉烯肺炎克雷伯菌的高流行率。通过详细研究肺炎克雷伯菌ST15，我们展示了这些菌株中所含耐药基因的重要性，这些菌株由直接进入或通过转诊进入两家医院的患者广泛携带。
医学研究理事会牛顿基金、科学技术部、惠康信托基金会、医学科学院、健康基金会以及剑桥生物医学研究中心国家健康与护理研究所。
