A genomic epidemiology study of multidrug-resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii in two intensive care units in Hanoi, Vietnam
Authors: Roberts Leah W. , Hoi Le Thi , Khokhar Fahad A. , Hoa Nguyen Thi , Van Giang Tran , Bui Cuong , Ninh Tran Hai , Co Dao Xuan , Binh Nguyen Gia , Long Hoang Bao , Huong Dang Thi , Bryan James E. , Herrick Archie , Feltwell Theresa , Nadjm Behzad , van Doorn H. Rogier , Parkhill Julian , Trung Nguyen Vu , Van Kinh Nguyen , Iqbal Zamin , Török M. Estée 
Published: December 2020

AbstractBackgroundVietnam has high rates of antimicrobial resistance (AMR) but limited capacity for genomic surveillance. This study used whole genome sequencing (WGS) to examine the prevalence and transmission of three key AMR pathogens in two intensive care units in Hanoi, Vietnam.MethodsA prospective surveillance study of all adults admitted to intensive care units (ICUs) at the National Hospital for Tropical Diseases (NHTD) and Bach Mai Hospital (BMH) was conducted between June 2017 and January 2018. Clinical and environmental samples were cultured on selective media, characterised using MALDI TOF MS, and illumina sequenced. Phylogenies based on the de novo assemblies (SPAdes) were constructed using Mafft (PARsnp), Gubbins and RAxML. Resistance genes were detected using Abricate against the NCBI database.Findings3,153 Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A. baumannii (global clone [GC]2, sequence types [ST]2, ST571) and K. pneumoniae (ST15, ST16, ST656, ST11, ST147) isolates. Colonisation was most common with E. coli (88.9%) followed by K. pneumoniae (62.4%). Of the E. coli, 91% carried a blaCTX-M variant, while 81% of K. pneumoniae isolates carried blaNDM (54%) and/or blaKPC (45%). Transmission analysis using single nucleotide polymorphisms (SNPs) identified 167 clusters involving 251 (68%) patients, in some cases involving patients from both ICUs. There were no significant differences between the lineages or AMR genes recovered between the two ICUs.InterpretationThis study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission prior to ICU admission in other healthcare settings or in the community.FundingThis work was funded by the Medical Research Council Newton Fund, United Kingdom; the Ministry of Science and Technology, Vietnam; and the Wellcome Trust, United Kingdom.Research in contextEvidence before this studyGlobally, antimicrobial resistance (AMR) is projected to cause 10 million deaths annually by 2050. Ninety percent of these deaths are expected to occur in low- and middle-income countries (LMICs), but attributing morbidity and mortality to AMR is difficult in the absence of comprehensive data. Whilst efforts have been made to improve AMR surveillance in these settings, this is often hampered by limited expertise, laboratory infrastructure and financial resources.Added value of this studyThis is the largest prospective surveillance study of three key AMR pathogens (E. coli, K. pneumoniae and A. baumannii) conducted in critical care settings in Vietnam. Sampling was restricted to patients who were colonised or infected with extended spectrum beta-lactamase (ESBL) producing and/or carbapenem-resistant organisms. Colonisation with more than one organism was very common, with multidrug-resistant (MDR) E. coli being predominant in stool samples. A small number of predominant lineages were identified for K. pneumoniae and A. baumannii, while the E. coli isolates were highly genetically diverse. A large number of genomic clusters were identified within the two ICUs, some of which spanned both ICUs. There were no significant differences between lineages or AMR genes between the two ICUs.Implications of all the available evidenceThis study found high rates of colonisation and infection with three key AMR pathogens in adults admitted to two Vietnamese ICUs. Whilst transmission was common within ICUs the finding of similar lineages and AMR genes in both ICUs suggests that dissemination of AMR occurs prior to ICU admission, either in referral hospitals or in community settings prior to hospital admission. Strategies to tackle AMR in Vietnam will need to account for this by extending surveillance more widely across hospital and community settings.