10.3389/fmicb.2018.01197.s001 Pieter W. Smit Pieter W. Smit Nicole Stoesser Nicole Stoesser Sreymom Pol Sreymom Pol Esther van Kleef Esther van Kleef Mathupanee Oonsivilai Mathupanee Oonsivilai Pisey Tan Pisey Tan Leakhena Neou Leakhena Neou Claudia Turner Claudia Turner Paul Turner Paul Turner Ben S. Cooper Ben S. Cooper Image_1_Transmission Dynamics of Hyper-Endemic Multi-Drug Resistant Klebsiella pneumoniae in a Southeast Asian Neonatal Unit: A Longitudinal Study With Whole Genome Sequencing.PDF Frontiers 2018 Klebsiella pneumoniae multidrug-resistance colonization whole genome sequencing neonatal unit 2018-06-19 11:14:36 Figure https://frontiersin.figshare.com/articles/figure/Image_1_Transmission_Dynamics_of_Hyper-Endemic_Multi-Drug_Resistant_Klebsiella_pneumoniae_in_a_Southeast_Asian_Neonatal_Unit_A_Longitudinal_Study_With_Whole_Genome_Sequencing_PDF/6606281 <p>Background:Klebsiella pneumoniae is an important and increasing cause of life-threatening disease in hospitalized neonates. Third generation cephalosporin resistance (3GC-R) is frequently a marker of multi-drug resistance, and can complicate management of infections. 3GC-R K. pneumoniae is hyper-endemic in many developing country settings, but its epidemiology is poorly understood and prospective studies of endemic transmission are lacking. We aimed to determine the transmission dynamics of 3GC-R K. pneumoniae in a newly opened neonatal unit (NU) in Cambodia and to address the following questions: what is the diversity of 3GC-R K. pneumoniae both within- and between-host; to what extent is high carriage prevalence driven by ward-based transmission; and to what extent can environmental contamination explain patterns of patient acquisition.</p><p>Methods: We performed a prospective longitudinal study between September and November 2013. Rectal swabs from consented patients were collected upon NU admission and every 3 days thereafter. Morphologically different colonies from swabs growing cefpodoxime-resistant K. pneumoniae were selected for whole-genome sequencing (WGS).</p><p>Results: One hundred and fifty-eight samples from 37 patients and 7 environmental sites were collected. 32/37 (86%) patients screened positive for 3GC-R K. pneumoniae and 93 colonies from 119 swabs were successfully sequenced. Isolates were resistant to a median of six (range 3–9) antimicrobials. WGS revealed high diversity; pairwise distances between isolates from the same patient were either 0–1 SNV or >1,000 SNVs; 19/32 colonized patients harbored K. pneumoniae colonies differing by >1000 SNVs. Diverse lineages accounted for 18 probable importations to the NU and nine probable transmission clusters involving 19/37 (51%) of screened patients. Median cluster size was five patients (range 3–9). Seven out of 46 environmental swabs (15%) were positive for 3GC-R K. pneumoniae. Environmental sources were plausible sources for acquisitions in 2/9 transmission clusters, though in both cases other patients were also plausible sources.</p><p>Conclusion: The epidemiology of 3GC-R K. pneumoniae was characterized by multiple introductions, high within- and between host diversity and a dense network of cross-infection, with half of screened neonates part of a transmission cluster. We found no evidence to suggest that environmental contamination was playing a dominant role in transmission.</p>