A genomic epidemiology study of multidrug-resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii in two intensive care units in Hanoi, Vietnam

Background Vietnam 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. Methods A 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. Findings 3,153 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 bla CTX-M variant, while 81% of K. pneumoniae isolates carried bla NDM (54%) and/or bla KPC (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. Interpretation This 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. Funding This 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. Evidence before this study Globally, 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 study This 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 evidence This 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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN18160232 https://doi.org/10.1186/ISRCTN18160232 ### Funding Statement Funding This work was funded by the Medical Research Council Newton Fund, United Kingdom; the Ministry of Science and Technology, Vietnam (HNQT/SPĐP/04.16) and the Wellcome Trust, United Kingdom. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the Scientific and Ethical Committees of the National Hospital for Tropical Diseases and Bach Mai Hospital and by the University of Cambridge Human Biology and Research Ethics Committee (reference: HBREC 2017.09). Written informed consent was obtained from the patient or from their relative prior to enrolment in the study. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Genome sequence data have been deposited in the European Nucleotide Archive (ENA) under the Bioproject PRJEB29424. A list of the sample accession numbers is available in Supplementary Dataset 1. Isolate genome assemblies (heterogenous sites masked and unmasked) are available on Figshare under the following DOI: 10.6084/m9.figshare.13303253, 10.6084/m9.figshare.13302728.