Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising patients at Siriraj hospital, Bangkok, Thailand from 2015 to 2017

BMC Infectious Diseases

Kanokorn Lerdlamyong¹  Teerawit Tangkoskul¹  Visanu Thamlikitkul²  Adhiratha Boonyasiri³  Kevin Nguyen⁴  Chris Greco⁴  Derrick E. Fouts⁴  Lauren M. Brinkac⁵  Elita Jauneikaite⁶ 

[1] Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand;Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand;NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College, London, UK;J. Craig Venter Institute, Rockville, MD, USA;J. Craig Venter Institute, Rockville, MD, USA;Noblis, Reston, VA, USA;NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College, London, UK;Department of Infectious Disease Epidemiology, School of Public Health, Imperial College, London, UK;

关键词: Klebsiella pneumoniae;    Enterobacteriaceae;    Antimicrobial resistance genes;    Patient outcomes;    Virulence genes;    Phylogenetics;   

DOI  :  10.1186/s12879-021-05790-9

来源: Springer

【 摘 要 】

BackgroundInfections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data.MethodsThe clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes.ResultsAltogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n = 18) and CPE-colonised patients who developed CPE infections during the study (n = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 (n = 15) and ST231 (n = 14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes.ConclusionsThis study has revealed the genomic features of colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.

【 授权许可】

CC BY